... Educators Search English Español Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth / For Parents / Your Child's Immunizations: ... cochlear implants. Why Are the PCV and PPSV Vaccines Recommended? Children younger than 2 years old, adults ...
... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its...
Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.
Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.
Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Ganaie, Feroze; Bhaskar, Arun; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Ravikumar, Kadahalli Lingegowda; Das, Ranjan Saurav; Mandal, Sutapa
Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.
van Werkhoven, Cornelis H; Hollingsworth, Rosalind C; Huijts, Susanne M; Bolkenbaas, Marieke; Webber, Chris; Patterson, Scott; Sanders, Elisabeth A M; Bonten, Marc J M
BACKGROUND: Herd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older
Mäkelä, P. Helena; Siber, George R; Klugman, Keith P
... of Streptococcus pneumoniae with Complement Proteins 83 Margaret K. Hostetter III. Clinical Disease and Epidemiology 8 Epidemiology, Diagnosis, and Treatment of Serious Pneumococcal Infections in Chi...
Öbrink-Hansen, Kristina; Søgaard, Ole S; Harboe, Zitta B
HIV-infected individuals have excess rates of invasive pneumococcal disease. We investigated risk factors for nasopharyngeal pneumococcal colonization at baseline and after 9 months in 96 HIV patients immunized twice with 7- valent pneumococcal conjugate vaccine ±1mg CPG 7909. In total, 22 patients...
Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate Vaccine (PCV13) and Pneumococcal Polysaccharide Vaccine (PPSV23) For children Administer PCV13 ...
Full Text Available The article describes the problem of pneumococcal infections (pneumonias, meningitis, otitis in children and adults. The modern opportunities of vaccinoprophylaxis and its usefulness in public health service are shown. The perspectives and questions on safety and effectiveness of pneumococcal conjugated 7-valent vaccine as the basic method of pneumococcal infections prophylaxis in infants and children from risk groups (with bronchial asthma, sickle-cell anemia, etc. are presented in details.Key words: children, pneumococcal infection, vaccination, pneumococcal conjugated 7-valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(4:79-83
Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A
Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.
Harboe, Zitta Barrella; Dalby, Tine; Weinberger, Daniel M
BACKGROUND: The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or ...
Hasan, Syed; Yousef, Mahmoud; Shridharani, Sachin
Polyvalent pneumococcal polysaccharide vaccine (Pneumovax, PPV) has been shown to substantially reduce the risk of Streptococcus pneumoniae infections in susceptible individuals. Side effects, such as mild local erythema, induration, pain and fever, have been reported with various frequencies. Rarely, systemic symptoms, including high fever, headache, nausea and photophobia, have been reported in the literature. This case report describes a 38-year-old male who developed severe and prolonged local and systemic symptoms necessitating hospitalization following a dose of pneumovax.
Full Text Available World Health Organization has recommended all countries to introduction of Pneumococcal Conjugate Vaccine (PCV in routine immunization schedule, especially those countries with higher rate of mortality in children. However, Islamic Republic of Iran and more than 50 other countries including Algeria, Antigua and Barbuda, Belarus, Belize, Bhutan, Bosnia and Herzegovina, Brunei Darussalam, Cabo Verde, Chad, China, Comoros, Cook Islands, Croatia, Cuba, Czech Republic, Democratic People's Republic of Korea, Dominica, Egypt, Equatorial Guinea, Estonia, Gabon, Grenada, Guinea, Haiti, India, Jamaica, Jordan, Malaysia, Maldives, Malta, Montenegro, Nauru, Poland, Romania, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Samoa, San Marino, Serbia, Seychelles, Slovenia, Somalia, South Sudan, Sri Lanka, Syrian Arab Republic, Tajikistan, Thailand, The former Yugoslav Republic of Macedonia, Timor-Leste, Tonga, Tunisia, Turkmenistan, Tuvalu, Ukraine, Vanuatu, and Viet Namhave not introduced PCV till April 2016.
Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita
The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults.
Brueggemann, Angela B; Pai, Rekha; Crook, Derrick W; Beall, Bernard
The heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the United States (US) in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990), but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s) at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny), recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.
Alharbi, N. S.; Al-Barrak, A. M.; Al-Moamary, M. S.; Zeitouni, M. O.; Idrees, M. M.; Al-Ghobain, M. O.; Al-Shimemeri, A. A.; Al-Hajjaj, Mohamed S.
Streptococcus pneumoniae (pneumococcus) is the leading cause of morbidity and mortality worldwide. Saudi Arabia is a host to millions of pilgrims who travel annually from all over the world for Umrah and the Hajj pilgrimages and are at risk of developing pneumococcal pneumonia or invasive pneumococcal disease (IPD). There is also the risk of transmission of S. pneumoniae including antibiotic resistant strains between pilgrims and their potential global spread upon their return. The country also has unique challenges posed by susceptible population to IPD due to people with hemoglobinopathies, younger age groups with chronic conditions, and growing problem of antibiotic resistance. Since the epidemiology of pneumococcal disease is constantly changing, with an increase in nonvaccine pneumococcal serotypes, vaccination policies on the effectiveness and usefulness of vaccines require regular revision. As part of the Saudi Thoracic Society (STS) commitment to promote the best practices in the field of respiratory diseases, we conducted a review of S. pneumoniae infections and the best evidence base available in the literature. The aim of the present study is to develop the STS pneumococcal vaccination guidelines for healthcare workers in Saudi Arabia. We recommend vaccination against pneumococcal infections for all children Saudi Arabia population <50 years of age, many of whom have risk factors for contracting pneumococcal infections. A section for pneumococcal vaccination before the Umrah and Hajj pilgrimages is included as well. PMID:27168856
Full Text Available Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death.
Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was maintained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.
Nurhonen, Markku; Auranen, Kari
Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children replacement through herd effects, the decrease among the older population is predicted to be much less (20-40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including
Full Text Available Invasive pneumococcal infection is the most frequent cause of death in patients with immunodeficiences. The antibiotics used previously for prevention purposes are not efficient enough due to the developing antibiotic resistance. Polysaccharide pneumococcal vaccines create short-lived immunity. The overview summarizes the experience of applying conjugated pneumococcal vaccines in patients with primary immunodeficiences, HIV infection, oncological and rheumatic diseases. Key words: pneumococcal infection, pneumococcal conjugated vaccines, children, immunosuppression. (Pediatric Pharmacology. – 2010; 7(5:18-23
Full Text Available In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0–84.6% in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE of PCVs and its impact in reducing pneumococcal diseases. A 1 : 3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%–84%; it was 69% (95% CI: 30%–88% against IPD and 77% (95% CI: 61%–87% against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage.
Echániz-Avilés Irma Gabriela
Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.html
Hansen, Nadja Skadkær; Byberg, Stine; Hervig Jacobsen, Lars
BACKGROUND: Measles vaccine (MV) may have non-specific beneficial effects for child health and particularly seems to prevent respiratory infections. Streptococcus pneumoniae is the leading cause of bacterial pneumonia among children worldwide, and nasopharyngeal colonization precedes infection....... OBJECTIVE: We investigated whether providing early MV at 18 weeks of age reduced pneumococcal colonization and/or density up to 9 months of age. METHOD: The study was conducted in 2013-2014 in Guinea-Bissau. Pneumococcal vaccine was not part of the vaccination program. Infants aged 18 weeks were block...
Studies evaluating a 9-valent PCV in South Africa and The Gambia reported a 72 - 77% reduction in vaccineserotype- specific invasive disease in vaccinated children. As many of the pneumococcal serotypes associated with antibiotic resistance are included in PCV, vaccination has also been associated with a reduction in ...
Taitel, Michael; Cohen, Ed; Duncan, Ian; Pegus, Cheryl
Older adults and persons with chronic conditions are at increased risk for pneumococcal disease. Severe pneumococcal disease represents a substantial humanistic and economic burden to society. Although pneumococcal vaccination (PPSV) can decrease risk for serious consequences, vaccination rates are suboptimal. As more people seek annual influenza vaccinations at community pharmacies, pharmacists have the ability to identify at-risk patients and provide PPSV. The objective of this study was to evaluate the impact of pharmacists educating at-risk patients on the importance of receiving a pneumococcal vaccination. Using de-identified claims from a large, national pharmacy chain, all patients who had received an influenza vaccination between August 1, 2010 and November 14, 2010 and who were eligible for PPSV were identified for the analysis. Based on the Advisory Committee on Immunization Practices recommendations, at-risk patients were identified as over 65 years of age or as aged 2-64 with a comorbid conditions. A benchmark medical and pharmacy claims database of commercial and Medicare health plan members was used to derive a PPSV vaccination rate typical of traditional care delivery to compare to pharmacy-based vaccination. Period incidence of PPSV was calculated and compared. Among the 1.3 million at-risk patients who were vaccinated by a pharmacist during the study period, 65,598 (4.88%) also received a pneumococcal vaccine. This vaccination rate was significantly higher than the benchmark rate of 2.90% (34,917/1,204,104; pvaccination rate (6.60%; 26,430/400,454) of any age group. Pharmacists were successful at identifying at-risk patients and providing additional immunization services. Concurrent immunization of PPSV with influenza vaccination by pharmacists has potential to improve PPSV coverage. These results support the expanding role of community pharmacists in the provision of wellness and prevention services. Copyright © 2011 Elsevier Ltd. All rights
Sowden, Evin; Mitchell, William S
Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p risk factors was confirmed as significant in determining vaccination status by logistic regression for both influenza (OR 10.89, p < 0.001) and streptococcus pneumoniae (OR 4.55, p = 0.002). The diagnosis of rheumatoid arthritis was also found to be a significant factor for pneumococcal vaccination (OR 5.1, p = 0.002). There was a negative trend suggesting that patients on major immunosuppressants are less likely to be immunised against pneumococcal antigen (OR 0.35, p = 0.067). Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.
Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn
This is the first case report of recurrent invasive pneumococcal disease (IPD), specifically, due to serotype 12F. The patient described here was vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) due to previous splenectomy, and an anti-pneumococcal IgG test concluded...
Vemer, P.; Postma, M.J.
Objectives: The Dutch National Immunization Program offers the 10-valent pneumococcal conjugate vaccine (PCV10). Also licensed for use in the infant population is the 13-valent PCV (PCV13). To update cost-effectiveness (CE) estimates of PCV13 over PCV10, using current epidemiological and economic
Tawfik, Kareem O; Ishman, Stacey L; Altaye, Mekibib; Meinzen-Derr, Jareen; Choo, Daniel I
Objectives (1) Describe longitudinal trends in annual prevalence of hospital admission for pediatric acute otitis media (AOM) and complications of AOM (CAOM) since introduction of pneumococcal vaccination in 2000 and (2) describe the longitudinal trend of prevalence of hospital admission for pneumococcal meningitis in children with AOM-related diagnoses in the postvaccination era. Study Design Retrospective analysis of Kids' Inpatient Database from 2000 to 2012. Setting Community, nonrehabilitation hospitals. Subjects and Methods To determine annual prevalence of admission for AOM/CAOM, nationally weighted frequencies of children aged otitis media, acute mastoiditis, suppurative labyrinthitis, and/or acute petrositis were collected. The frequency of coexisting pneumococcal meningitis diagnoses among these patients was also collected. Trend analysis of prevalences of admission for AOM/CAOM and for pneumococcal meningitis occurring in the setting of AOM/CAOM from 2000 to 2012 was performed. Results Between 2000 and 2012, annual prevalence of admission for AOM/CAOM decreased from 3.956 to 2.618 per 100,000 persons ( P < .0001) (relative risk reduction 34%). Declines in admission prevalence were most pronounced in children <1 year of age (from 22.647 to 8.715 per 100,000 persons between 2000 and 2012, P < .0001) and 1 to 2 years of age (from 13.652 to 5.554 per 100,000 persons between 2000 and 2012, P < .0001). For all ages, the admission prevalence for pneumococcal meningitis and concomitant AOM/CAOM decreased (from 1.760 to 0.717 per 1,000,000 persons, P < .0001) over the study period. Conclusions The prevalence of hospital admission for pediatric AOM/CAOM has declined since the advent of pneumococcal vaccination. Admission rates for pneumococcal meningitis with AOM/CAOM have similarly declined.
Hak, Eelko; Shea, Kimberly M.; Jick, Susan S.
Since implementation of infant immunization with 7-valent pneumococcal conjugate vaccine (PCV7), increased rates of pneumococcal pneumonia have been reported among adults. Using a cohort of mother-infant pairs identified from the General Practice Research Database in the UK we found that from 2006
Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond
Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information
Jean-Baptiste Le Meur
Full Text Available Background: In 2000, an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of Quebec. A mass immunization campaign was implemented in the spring of 2002, targeting persons ≥5 years of age and using the 23-valent pneumococcal polysaccharide vaccine (PPSV23. At the same time, the 7-valent pneumococcal conjugate vaccine (PCV7 was introduced into the routine immunization programme of infants, with catch-up for children up to 4 years of age. Objectives: To describe the epidemiology of invasive pneumococcal disease (IPD in relation to PPSV23 and PCV7 use. Study design and methods: Retrospective analysis of IPD cases identified by the Quebec public health laboratory during the period 1997–2010. Results: A total of 82 IPD cases were identified during the study period. In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign but breakthrough cases continued to occur. Following PCV7 use in children, there was a decrease in the incidence of vaccine-type IPD and replacement by other serotypes in adults. In children, a marked decrease in the annual incidence of serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000 in 1997–2001 vs. 10/100,000 in 2004–2010 (p<0.01. Concomitantly, the incidence of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to 109/100,000 (p=0.11. Conclusion: The mass immunization campaign using the PPSV23 in 2002 and the introduction of PCV7 for the routine immunization of infants induced important modifications in the epidemiology of IPD. IPD rates in Nunavik remain much higher than in the southern part of the province both in children and adults. More effective pneumococcal vaccines are needed to eliminate geographic disparities in IPD risk.
Mitchell William S
Full Text Available Abstract Background Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. Method We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Results Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p Conclusion Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.
Cernuschi, Tania; Furrer, Eliane; Schwalbe, Nina; Jones, Andrew; Berndt, Ernst R; McAdams, Susan
Markets for life-saving vaccines do not often generate the most desired outcomes from a public health perspective in terms of product quantity, quality, affordability, programmatic suitability and/or sustainability for use in the lowest income countries. The perceived risks and uncertainties about sustainably funded demand from developing countries often leads to underinvestment in development and manufacturing of appropriate products. The pilot initiative Advance Market Commitment (AMC) for pneumococcal vaccines, launched in 2009, aims to remove some of these market risks by providing a legally binding forward commitment to purchase vaccines according to predetermined terms. To date, 14 countries have already introduced pneumococcal vaccines through the AMC with a further 39 countries expected to introduce before the end of 2013.This paper describes early lessons learnt on the selection of a target disease and the core design choices for the pilot AMC. It highlights the challenges faced with tailoring the AMC design to the specific supply situation of pneumococcal vaccines. It points to the difficulty - and the AMC's apparent early success - in establishing a long-term, credible commitment in a constantly changing unpredictable environment. It highlights one of the inherent challenges of the AMC: its dependence on continuous donor funding to ensure long-term purchases of products. The paper examines alternative design choices and aims to provide a starting point to inform discussions and encourage debate about the potential application of the AMC concept to other fields.
Zhang Jian Shayne F
Full Text Available Abstract Background Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA vaccine offering protection for all serotypes. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results The experts expressed very high level of optimism (over 80% that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9
Full Text Available This article presents the review of results of International conference on pneumococcal conjugated vaccines. Main results of international experience in the field of control of pneumococcal infection spreading are analyzed. Authors present modern data of clinical and economic effectiveness and safety of pneumococcal conjugated vaccine RCV-7, and describe experience of administration of vaccines of next generation – PCV-10 and PCV-13.Key words: children, pneumococcal infections, prophylaxis, vaccines.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(1:130-134
M. S. Naumtseva
Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA.
S. V. Il'ina
Full Text Available Study aim: analyzing the results of pneumococcal infection vaccination conducted to reduce infantile morbidity and mortality in 2011-2012 at the expenses of the Irkutsk municipal budget. Patients and methods. Vaccination using the 7- and 13-valent pneumococcal conjugated vaccine was conducted for more than 700 risk group children: premature infants, children with congenital heart diseases or bronchopulmonary dysplasia from 2 months to 2 years of age. 193 vaccinated children had been observed for 1.5 years. 30% of premature infants and 46% of children with congenital heart diseases were vaccinated using the PCV7/PCV13 vaccine at the age of 2-6 months, 52 and 40% - at the age of 7-11 months, accordingly. The PCV7/PCV13 vaccine was administered together with other vaccines of the national preventive vaccination calendar in 65% of cases. Results. Rate of general post-vaccinal reactions (body temperature increase from 37.6 to 38.0oC – 4%; no local reactions were registered. No other unfavorable phenomena were noted in the post-vaccinal period. No cases of pneumonia, meningitis, acute otitis media and bronchoobstructive syndrome were registered within the observation period. Conclusions: pneumococcal infection vaccination of premature infants with congenital heart diseases and bronchopulmonary dysplasia conducted in Irkutsk proved high efficacy and safety of the used vaccine – PCV7/PCV13.
Full Text Available A new pneumococcal conjugate vaccine is currently undergoing advanced clinical evaluation prior to its planned introduction in Cuba. The implementation of the pneumococcal vaccination strategy has been designed with consideration of the need to maximize both its direct and indirect effects. A novel approach is suggested, which addresses preschool children as the first-line target group to generate herd immunity in infants and to have an impact on transmission at the community level. The clinical evaluation pipeline is described herein, including evaluations of effectiveness, cost-effectiveness, and impact. The scientific contribution of the Cuban strategy could support a paradigm shift from individual protection to a population effect based on a rigorous body of scientific evidence.
Vučina, V Višekruna; Filipović, S Kurečić; Kožnjak, N; Stamenić, V; Clark, A D; Mounaud, B; Blau, J; Hoestlandt, C; Kaić, B
Pneumococcus is a known cause of meningitis, pneumonia, sepsis, and acute otitis media in children and adults globally. Two new vaccines for children have the potential to prevent illness, disability, and death, but these vaccines are expensive. The Croatian Ministry of Health has considered introducing the vaccine in the past, but requires economic evidence to ensure that the limited funds available for health care will be used in the most effective way. Croatia appointed a multidisciplinary team of experts to evaluate the cost-effectiveness of introducing pneumococcal conjugate vaccination (PCV) into the national routine child immunization program. Both 10-valent and 13-valent PCV (PCV10 and PCV13) were compared to a scenario assuming no vaccination. The TRIVAC decision-support model was used to estimate cost-effectiveness over the period 2014-2033. We used national evidence on demographics, pneumococcal disease incidence and mortality, the age distribution of disease in children, health service utilization, vaccine coverage, vaccine timeliness, and serotype coverage. Vaccine effectiveness was based on evidence from the scientific literature. Detailed health care costs were not available from the Croatian Institute for Health Insurance at the time of the analysis so assumptions and World Health Organization (WHO) estimates for Croatia were used. We assumed a three-dose primary vaccination schedule, and an initial price of US$ 30 per dose for PCV10 and US$ 35 per dose for PCV13. We ran univariate sensitivity analyses and multivariate scenario analyses. Either vaccine is estimated to prevent approximately 100 hospital admissions and one death each year in children younger than five in Croatia. Compared to no vaccine, the discounted cost-effectiveness of either vaccine is estimated to be around US$ 69,000-77,000 per disability-adjusted life-years (DALYs) averted over the period 2014-2033 (from the government or societal perspective). Only two alternative scenarios
Full Text Available Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. In Uganda, PCV was launched in 2014, but baseline data is lacking for pneumococcal serotypes in carriage.To study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in Uganda.Three cross-sectional pneumococcal carriage surveys were conducted in 2008, 2009 and 2011, comprising respectively 150, 587 and 1024 randomly selected children aged less than five years from the Iganga/Mayuge Health and Demographic Surveillance Site. The caretakers were interviewed about illness history of the child and 1723 nasopharyngeal specimens were collected. From these, 927 isolates of S. pneumoniae were serotyped.Overall, the carriage rate of S. pneumoniae was 56% (957/1723. Pneumococcal carriage was associated with illness on the day of the interview (OR = 1.50, p = 0.04. The most common pneumococcal serotypes were in descending order 19F (16%, 23F (9%, 6A (8%, 29 (7% and 6B (7%. One percent of the strains were non-typeable. The potential serotype coverage rate for PCV10 was 42% and 54% for PCV13.About half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs.
Kim, Sun-Young; Lee, Gene; Goldie, Sue J
Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars) per disability-adjusted life year (DALY) averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Assuming 90% coverage, a program using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Based on the information available now, infant PCV vaccination would be expected to reduce pneumococcal diseases caused by S. pneumoniae in The Gambia
Full Text Available Abstract Background Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7, but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. Methods We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars per disability-adjusted life year (DALY averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Results Assuming 90% coverage, a program using a 9-valent PCV (PCV9 would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine, compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Conclusions Based on the information available now, infant PCV vaccination would be expected to reduce
Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S
Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children vaccine (PCV7) into the Danish routine...... children vaccination....... immunization programme October 2007. Methods: Clinical and microbiological records on cases of IPD in children children
Tatiane E. Hirose
Conclusion: Even after a short time of use, the 10‐valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine.
Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S
Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine...... immunization programme October 2007. Methods: Clinical and microbiological records on cases of IPD in children Hospital, Denmark 1996-2007, were retrospectively reviewed. Results: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children
Conclusion: Taiwanese elderly adults with COPD, even in advanced age, can mount a significant antibody response to pneumococcal polysaccharide vaccine. This study may support the existing recommendation that pneumococcal vaccine be offered to persons ≥ 65 years old with COPD. [J Formos Med Assoc 2007;106(3: 196-203
Diana C Otczyk
Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia. The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children. However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement. The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes. Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries. The next generation of pneumococcal vaccines have advanced to clinical trials.
Full Text Available Abstract Background Previous studies have shown influenza vaccine uptake in UK nursing home residents to be low. Very little information exists regarding the uptake of pneumococcal vaccine in this population. The formulation of policies relating to the vaccination of residents has been proposed as a simple step that may help improve vaccine uptake in care homes. Methods A postal questionnaire was sent to matrons of all care homes with nursing within the Greater Nottingham area in January 2006. Non respondents were followed up with up to 3 phone calls. Results 30% (16/53 of respondents reported having a policy addressing influenza vaccination and 15% (8/53 had a policy addressing pneumococcal vaccination. Seasonal influenza vaccine coverage in care homes with a vaccination policy was 87% compared with 84% in care homes without a policy (p = 0.47. The uptake of pneumococcal vaccination was found to be low, particularly in care homes with no vaccination policy. Coverage was 60% and 32% in care homes with and without a vaccination policy respectively (p = 0.06. This result was found to be statistically significant on multivariate analysis (p = 0.03, R = 0.46 Conclusion The uptake of influenza vaccine among care home residents in the Nottingham region is relatively high, although pneumococcal vaccine uptake is low. This study shows that there is an association between pneumococcal vaccine uptake and the existence of a vaccination policy in care homes, and highlights that few care homes have vaccination policies in place.
Tatiane E. Hirose
Full Text Available Objectives: To evaluate the possible effects of the introduction of the pneumococcal conjugate 10-valent vaccine schedule in the state of Parana on pneumococcal meningitis cases and to assess the distribution of serotypes among cases. Method: Cross-sectional study with retrospective data collection of cases of pneumococcal meningitis in the state of Paraná reported to Sistema de Informação de Agravos de Notificação (SINAN, from 1998 to 2011. A total of 1,339 cases of pneumococcal meningitis were analyzed; 1,205 cases from the pre-vaccine period (1998-2009 were compared to 134 cases from the post-vaccine period (2010-2011. Descriptive and comparative statistical analyses (chi-squared test and prevalence ratio were performed using JMP 5.1.2 statistical software (JMP Statistical Discovery, North Carolina, USA and EPI INFO 6 (Centers for Disease Control and Prevention, Georgia, EUA. Results: There was a significant reduction in the mean rates of incidence and mortality in the general population. The analysis of cases in the pre- and post-vaccination periods in the age groups covered by vaccination (younger than 2 years showed significant reductions in incidence rates (6.01 cases/100,000 to 2.49 cases/100,000 individuals and mortality (1.85 cases/100,000 population to 0.47 cases/100,000 population, while the mean lethality rate did not change significantly. There was a significant reduction in cases whose serotypes are included in the vaccine (80.7% to 53.3%. Conclusion: Even after a short time of use, the 10-valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine. Resumo: Objetivos: Avaliar os possíveis efeitos da introdução da vacina pneumocócica conjugada 10 valente no calendário vacinal no Paraná sobre os casos de meningite pneumocócica; avaliar a distribuição dos
Caldwell, Ronald; Roberts, Craig S; An, Zhijie; Chen, Chieh-I; Wang, Bruce
China has experienced several severe outbreaks of influenza over the past century: 1918, 1957, 1968, and 2009. Influenza itself can be deadly; however, the increase in mortality during an influenza outbreak is also attributable to secondary bacterial infections, specifically pneumococcal disease. Given the history of pandemic outbreaks and the associated morbidity and mortality, we investigated the cost-effectiveness of a PCV7 vaccination program in China from the context of typical and pandemic influenza seasons. A decision-analytic model was employed to evaluate the impact of a 7-valent pneumococcal vaccine (PCV7) infant vaccination program on the incidence, mortality, and cost associated with pneumococcal disease during a typical influenza season (15% flu incidence) and influenza pandemic (30% flu incidence) in China. The model incorporated Chinese data where available and included both direct and indirect (herd) effects on the unvaccinated population, assuming a point in time following the initial introduction of the vaccine where the impact of the indirect effects has reached a steady state, approximately seven years following the implementation of the vaccine program. Pneumococcal disease incidence, mortality, and costs were evaluated over a one year time horizon. Healthcare costs were calculated using a payer perspective and included vaccination program costs and direct medical expenditures from pneumococcal disease. The model predicted that routine PCV7 vaccination of infants in China would prevent 5,053,453 cases of pneumococcal disease and 76,714 deaths in a single year during a normal influenza season.The estimated incremental-cost-effectiveness ratios were ¥12,281 (US$1,900) per life-year saved and ¥13,737 (US$2,125) per quality-adjusted-life-year gained. During an influenza pandemic, the model estimated that routine vaccination with PCV7 would prevent 8,469,506 cases of pneumococcal disease and 707,526 deaths, and would be cost-saving. Routine
Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive ...
Rousseau, Louise; Guay, Maryse; Archambault, Denis; El m'ala, Zahra; Abdelaziz, Nadia
Despite the implementation of a Quebec immunization program against influenza and pneumococcal disease (PQIIP), vaccine coverage has remained low. There have been many studies on personal barriers to vaccination, but few have explored other kinds of barriers. To explore the presence of barriers in relation to the organization of the health care system and to propose recommendations for increasing vaccine coverage. Within a mixed protocol, a phone survey of 996 people in the target population and a case study implicating the follow-up of the PQIIP with all the site and actor categories via 43 semistructured interviews and 4 focus groups were realized. Survey data underwent a descriptive statistical analysis. Qualitative analysis followed the Miles and Huberman approach. The results indicate the presence of barriers with regard to information accessibility. These include access to: the physicians' recommendation, knowledge of the efficacy or the security of vaccines, and admissibility of clients to the PQIIP. Organizational barriers were also found to limit access to vaccination, especially in terms of restricted choices of time and location. Coordination and incentives mechanisms are not optimal. Removal of organizational barriers depends more on strategic rather than structural factors. Addressing organizational barriers should be an important component of strategies aimed at improving vaccine coverage. Public health authorities should focus on strategic management of the information and inter-organizational environment.
... very sick. It causes blood infections, pneumonia, and meningitis, mostly in young children. (Meningitis... have many causes, and PCV13 only works against the types of pneumococcal bacteria targeted by the... the parent or legal representative in the case of a child) receiving vaccines covered under the...
Full Text Available Abstract Background The 23-valent polysaccharide pneumococcal vaccine (PPV is currently recommended in elderly and high-risk adults. However, its efficacy in preventing pneumococcal infections remains controversial. This study assessed the clinical effectiveness of vaccination against invasive pneumococcal disease (IPD among people over 60 years. Methods Population-based case-control study that included 88 case patients over 60 years-old with a laboratory-confirmed IPD (bacteraemic pneumonia, meningitis or sepsis and 176 outpatient control subjects who were matched by primary care centre, age, sex and risk stratum. Adjusted odds ratios (ORs for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was estimated as (1 - OR ×100. Results Pneumococcal vaccination rate was significantly lower in cases than in control subjects (38.6% vs 59.1%; p = 0.002. The adjusted vaccine effectiveness was 72% (OR: 0.28; 95% CI: 0.15-0.54 against all IPD and 77% (OR: 0.23; 95% CI: 0.08-0.60 against vaccine-type IPD. Vaccination was significantly effective against all IPD in both age groups: 60-79 years-old (OR 0.32; 95% CI: 0.14-0.74 and people 80 years or older (OR: 0.29; 95% CI: 0.09-0.91. Vaccination appears significantly effective as for high-risk immunocompetent subjects (OR: 0.29; 95% CI: 0.11-0.79 as well as for immunocompromised subjects (OR: 0.12; 95% CI: 0.03-0.53. Conclusion These findings confirm the effectiveness of the 23-valent PPV against IPD, and they also support the benefit of vaccination in preventing invasive infections among high-risk and older people.
Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe
Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international
Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C
Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody
Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D
Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.
Christenson, Brith; Pauksen, Karlis; Sylvan, Staffan P E
The present prospective study was conducted from 2003-2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area.The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS) even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. In 2003, the total study population was 41,059, of which 12,907 (31%) received influenza vaccine of these, 4,447 (11%) were administered the pneumococcal vaccine. In 2004, 14,799 (34%) individuals received the influenza vaccine and 8,843 (21%) the pneumococcal vaccine and in 2005 16,926 (39%) individuals were given the influenza vaccine and 12,340 (28%) the pneumococcal vaccine.Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine). Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age). For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75-84-year old age group and in all age-groups during the influenza season 2005. The present study confirmed the
Sylvan Staffan PE
Full Text Available Abstract Background The present prospective study was conducted from 2003–2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area. The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. Results In 2003, the total study population was 41,059, of which 12,907 (31% received influenza vaccine of these, 4,447 (11% were administered the pneumococcal vaccine. In 2004, 14,799 (34% individuals received the influenza vaccine and 8,843 (21% the pneumococcal vaccine and in 2005 16,926 (39% individuals were given the influenza vaccine and 12,340 (28% the pneumococcal vaccine. Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine. Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age. For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75–84-year old age group and in all age-groups during the influenza
Full Text Available An experience of immunization with pneumococcal conjugated 7-valent vaccine Prevenar in 234 children under 5 years old with different state of health was analyzed. There were no any severe reactions, postvaccinal complications or local reactions to the vaccine injection. Mild and moderate postvaccinal reactions were detected in 3,4% (n = 8 of children. The vaccine can be used in children under 5 years old.Key words: children, vaccination, pneumococcal conjugated 7-valent vaccine, safety.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:119-123
Dominguez, Angela; Salleras, Lluis; Fedson, David S; Izquierdo, Conchita; Ruiz, Laura; Ciruela, Pilar; Fenoll, Asuncion; Casal, Julio
Observational studies offer an approach to evaluating the effectiveness of vaccination programs. We evaluated the effectiveness of a 23-valent pneumococcal vaccination program for elderly people in Catalonia, Spain, in a matched-set case-control study. We identified 149 cases of invasive pneumococcal disease among patients aged > or =65 years who were hospitalized in 12 large hospitals in Catalonia during the period of 1 January 2001 through 31 March 2002. We selected 2 hospital control patients and 1 outpatient control subject for each case patient, matching on the basis of age and underlying medical conditions. We obtained their pneumococcal vaccination histories and used conditional logistic regression to determine effectiveness of vaccination. Among all 149 cases of invasive pneumococcal disease, 131 (87.9%) were caused by vaccine or vaccine-related serotypes. In the adjusted analysis, overall effectiveness of vaccination against infections due to all serotypes was 70% (95% confidence interval [CI], 48%-82%). Among immunocompetent subjects with or without high-risk conditions, effectiveness of vaccination was 76% (95% CI, 51%-88%), but among immunocompromised subjects it was 50% (95% CI, -44% to 82%). Among subjects with infections due to vaccine or vaccine-related serotypes, effectiveness of vaccination was 72% (95% CI, 50%-85%) overall and 78% (95% CI, 50%-90%) in those who were immunocompetent, but it was only 46% (95% CI, -54% to 81%) in those who were immunocompromised. Overall effectiveness of vaccination was 65% (95% CI, 35%-81%) during the noninfluenza period. Pneumococcal vaccination was effective in preventing invasive pneumococcal disease among all elderly persons in Catalonia. Effectiveness was greater in immunocompetent persons, most of whom had underlying high-risk conditions. The number of subjects was too small to determine whether vaccination was effective in those who were immunocompromised.
PURPOSE AND OBJECTIVES: The patients using immunosuppressive agents are considered at high risk for acquiring different infections. Accordingly, international guidelines recommend vaccinating such patients against influenza and pneumococcal organisms. The aims of this study were two-fold: (1) to assess the influenza and pneumococcal vaccination uptake among our rheumatology outpatients who are immunosuppressed; (2) to identify the factors influencing immunisation uptake among our sample of patients.
Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13 Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23 Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ
Full Text Available Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against Streptococcus pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23 and 13-valent pneumococcal conjugate vaccine (PCV13. Until recently, the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults aged 65 years or older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials that evaluated the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. Both studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo.
Invasive pneumococcal disease : Clinical outcomes and patient characteristics 2-6 years after introduction of 7-valent pneumococcal conjugate vaccine compared to the pre-vaccine period, the Netherlands
Wagenvoort, Gertjan H J; Sanders, Elisabeth A M; Vlaminckx, Bart J.; Elberse, Karin E.; de Melker, Hester E.; van der Ende, Arie; Knol, Mirjam J.
Background Implementation of 7-valent pneumococcal conjugate vaccine (PCV7) in the Dutch national immunization program for infants led to a shift from vaccine to non-vaccine serotypes in invasive pneumococcal disease (IPD) in all age groups. We studied the impact of the serotype shift on clinical
Bergman, Annika; Hjelmgren, Jonas; Ortqvist, Ake
The 7-valent pneumococcal conjugate vaccine (PCV-7) has proved to be highly effective against invasive pneumococcal disease and has also provided some protection against all-cause pneumonia and acute otitis media. The objective of this study was to evaluate the projected health benefits, costs...... of pneumococcal septicaemia among adults. The incremental cost per QALY and LY gained was estimated to Euro 29,200 and Euro 51,400, respectively. When herd immunity was accounted for, the cost per QALYand LY gained was estimated to Euro 5500 and Euro 6600, respectively. Thus, the health benefits of a national...... and cost-effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine compared with no vaccination, in all infants in Sweden, taking herd immunity into account. A Markov model was used and a hypothetical birth cohort was simulated for a lifelong perspective. The results show...
van Gils, E.J.M.; Hak, E.; Veenhoven, R.H.; Rodenburg, G.D.; Bogaert, D.; Bruin, J.P.; van Alphen, L.
Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the
Kim, John S; Laskowich, Erin R; Arumugham, Rasappa G; Kaiser, Raymond E; MacMichael, Gregory J
A simple and sensitive gas chromatographic method was designed for quantitative analysis of Streptococcus pneumoniae capsular polysaccharides, activated polysaccharides, and polysaccharide conjugates. Pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharide or conjugate were subjected to methanolysis in 3N hydrochloric acid in methanol followed by re-N-acetylation and trimethylsilylation. Derivatized samples were chromatographed and detected using gas chromatography with mass selective detector. Gas chromatographic results were compared with colorimetric values with agreement of 92 to 123% over the range of all samples tested. Monosaccharides released during methanolysis included hexoses, uronic acids, 6-deoxy-hexoses, amino sugars, and alditols. Quantitative recovery of monosaccharides was achieved for all serotypes by the use of a single methanolysis, derivatization, and chromatography procedure. Response factors generated from authentic monosaccharide standards were used for quantitation of pneumococcal polysaccharides and conjugates with confirmation of peak assignments by retention time and mass spectral analysis. This method allows saccharide quantitation in multivalent pneumococcal vaccine intermediates and final drug products with low-level detection (10 pg) and peak purity.
Sutton, Karyn L.; Banks, H. T.; Castillo-Chavez, Carlos
The design and evaluation of epidemiological control strategies is central to public health policy. While inverse problem methods are routinely used in many applications, this remains an area in which their use is relatively rare, although their potential impact is great. We describe methods particularly relevant to epidemiological modeling at the population level. These methods are then applied to the study of pneumococcal vaccination strategies as a relevant example which poses many challenges common to other infectious diseases. We demonstrate that relevant yet typically unknown parameters may be estimated, and show that a calibrated model may used to assess implemented vaccine policies through the estimation of parameters if vaccine history is recorded along with infection and colonization information. Finally, we show how one might determine an appropriate level of refinement or aggregation in the age-structured model given age-stratified observations. These results illustrate ways in which the collection and analysis of surveillance data can be improved using inverse problem methods. PMID:20209093
Smith, Jennifer G; Metzger, Nicole L
Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post-intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4-month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the
Indianara Maria Grando
Full Text Available The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009 and post-vaccination (2011-2012 periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.
Full Text Available Abstract Background In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV at 18 months of age. This study presents carriage serotypes following this schedule. Methods We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs in 2003 and 2005. Nasal secretions were collected and processed according to published methods. Results 902 children (mean age 25 months living in 29 communities in 2003 and 818 children (mean age 35 months in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL strains (15% overall was detected in serotypes (descending order 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL strains (5% overall, was detected in serotypes (descending order 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C. Conclusion Pneumococcal carriage remains high (~80% in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined
Harboe, Zitta B; Valentiner-Branth, Palle; Ingels, Helene
A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction...... of children suspected to present with a vaccine failure. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number) and 105 (55%) caused by one...... of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F...
Tinevimbo Shiri, DrPhD
Full Text Available Summary: Background: The full extent to which childhood pneumococcal conjugate vaccines (PCV can indirectly reduce illness in unvaccinated populations is not known. We aimed to estimate the magnitude and timing of indirect effects of PCVs on invasive pneumococcal disease. Methods: In this systematic review and meta-analysis, we searched bibliographic databases for non-randomised quasi-experimental or observational studies reporting invasive pneumococcal disease changes following PCV introduction in unvaccinated populations (studies published Sept 1, 2010, to Jan 6, 2016, updating the previous systematic review of the same topic (studies published Jan 1, 1994, to Sept 30, 2010. Two reviewers extracted summary data by consensus. We used a Bayesian mixed-effects model to account for between-study heterogeneity to estimate temporal indirect effects by pooling of invasive pneumococcal disease changes by serotype and serogroup. Findings: Data were extracted from 70 studies included in the previous review and 172 additional studies, covering 27 high-income and seven middle-income countries. The predicted mean times to attaining a 90% reduction in invasive pneumococcal disease were 8·9 years (95% credible interval [CrI] 7·8–10·3 for grouped serotypes contained in the seven-valent PCV (PCV7, and 9·5 years (6·1–16·6 for the grouped six additional serotypes contained in the 13-valent PCV (PCV13 but not in PCV7. Disease due to grouped serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV23 decreased at similar rates per year in adults aged 19–64 years (relative risk [RR] 0·85, 95% CrI 0·75–0·95 and 65 years and older (0·87, 0·84–0·90. However, we noted no changes in either group in invasive pneumococcal disease caused by the additional 11 serotypes covered by PPV23 but not PCV13. Interpretation: Population childhood PCV programmes will lead, on average, to substantial protection across the whole population
Lai, Zengzu; Schreiber, John R
Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.
Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard
BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients...... with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination...... with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher...
Demirdogen Cetinoglu, Ezgi; Uzaslan, Esra; Sayıner, Abdullah; Cilli, Aykut; Kılınc, Oguz; Sakar Coskun, Aysın; Hazar, Armağan; Kokturk, Nurdan; Filiz, Ayten; Polatli, Mehmet
Previous reports have shown that vaccination rates of adult at-risk populations are low in Turkey. There are differing reports with regards to the effectiveness of the influenza and the pneumococcal polysaccharide vaccine (PPSV23) on the clinical outcomes of community acquired pneumonia (CAP). The purpose of this study was to analyze the influenza (FV) and pneumococcal vaccination (PV) status, the factors that influence the receipt of influenza/pneumococcal vaccine and the effects of prior vaccination on the clinical outcomes in adults hospitalized with CAP. Patients hospitalized with CAP between March 2009 and October 2013 and registered at the web-based Turkish Thoracic Society Pneumonia Database (TURCAP) were included in this multicentric, observational study. Of a total of 787 cases, data were analyzed for 466 patients for whom self-reported information on PV and FV was available. In this adult population with CAP, the vaccination rate with both the pneumococcal and influenza vaccines was found to be 6%. Prior FV was found to be the sole variable that was associated with the receipt of PV [OR 17.8, 95% CI (25-75:8.56-37.01), p pneumonia severity index (PSI) score ≥ 90, CURB-65 score ≥3 and multilobar involvement, but not the vaccination status, were identified as independent determinants of ICU admission. This study showed that, among patients hospitalized with CAP, the FV and/or PV rates are low. Prior vaccination does not appear to significantly affect the clinical outcomes.
A. V. Rudakova
Full Text Available Aim: cost-effectiveness assessment and budget impact analysis for 13-valent pneumococcal conjugate vaccine (PCV13 in infant immunization program in Russian Federation. Materials and methods: 10 year modeling with social perspective (direct medical and indirect costs and life expectancy with discounting by 3,5% per year and population effect based on results of clinical studies, global PCV13 use and Russian epidemiological data has been established. Budget impact has been analyzed without discounting. Direct effect was assessed by influence on pneumococcal meningitis, bacteremia, pneumonia and acute otitis media (AOM incidence, population effect — by pneumococcal meningitis and hospitalized all-cause pneumonia incidence. Results: Possible PCV13 effectiveness was estimated as 76,6% for invasive pneumococcal diseases (IPD and 23,7% for hospitalized cases of AOM. Vaccination (per 100 000 vaccinated infants can prevent 13,8 lethal cases in vaccinated population and 171,1 — in unvaccinated population. Cost-effectiveness ratio for PCV13 is estimated as 32,400 rubles / LYG and 32,400 rubles / QALY. Cost of 1 lethal case prevention is 140 100 rubles, additional cost for 10 years is 111,5 rubles per child. Conclusions: PCV13 mass vaccination of infants in Russian Federation is highly cost-effective and will significantly cut expenses due to pneumococcal diseases treatment.
Leach, Amanda Jane; Wigger, Christine; Andrews, Ross; Chatfield, Mark; Smith-Vaughan, Heidi; Morris, Peter Stanley
In 2001 when 7-valent pneumococcal conjugate vaccine (PCV7) was introduced, almost all (90%) young Australian Indigenous children living in remote communities had some form of otitis media (OM), including 24% with tympanic membrane perforation (TMP). In late 2009, the Northern Territory childhood vaccination schedule replaced PCV7 with 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10). We conducted regular surveillance of all forms of OM in children in remote Indigenous communities between September 2008 and December 2012. This analysis compares children less than 36 months of age who received a primary course of at least two doses of PCV7 or PHiD-CV10, and not more than one dose of another pneumococcal vaccine. Mean ages of 444 PCV7- and 451 PHiD-CV10-vaccinated children were 20 and 18 months, respectively. Bilaterally normal middle ears were detected in 7% and 9% respectively. OM with effusion was diagnosed in 41% and 51% (Risk Difference 10% [95% Confidence Interval 3 to 17] p = 0.002), any suppurative OM (acute OM or any TMP) in 51% versus 39% (RD -12% [95% CI -19 to -5] p = 0.0004], and TMP in 17% versus 14% (RD -3% [95% CI -8 to 2] p = 0.2), respectively. Multivariate analyses described a similar independent negative association between suppurative OM and PHiD-CV10 compared to PCV7 (Odds Ratio = 0.6 [95% CI 0.4 to 0.8] p = 0.001). Additional children in the household were a risk factor for OM (OR = 2.4 [95% CI 2 to 4] p = 0.001 for the third additional child), and older age and male gender were associated with less disease. Other measured risk factors were non-significant. Similar clinical results were found for children who had received non-mixed PCV schedules. Otitis media remains a significant health and social issue for Australian Indigenous children despite PCV vaccination. Around 90% of young children have some form of OM. Children vaccinated in with PHiD-CV10 had less suppurative OM than
van Deursen, A. M.M.; Schurink-van't Klooster, Tessa M; Man, W. H.; van de Kassteele, J.; van Gageldonk-Lafeber, Arianne B; Bruijning-Verhagen, P. C.J.L.; de Melker, Hester E.; Sanders, E. A.M.; Knol, Mirjam J.
Background The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the
Jiang, Yiling; Gauthier, Aline; Keeping, Sam; Carroll, Stuart
Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits.
Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products
May, J.C.; Rey, L.; Lee, C.-J.; Arciniega, Juan
Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine
Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products
May, J.C. E-mail: firstname.lastname@example.org; Rey, L. E-mail: email@example.com; Lee, C.-J.; Arciniega, Juan
Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.
Icardi, G; Sticchi, L; Bagnasco, A; Iudici, R; Durando, P
Streptococcus pneumoniae (SP) is a leading cause of morbidity and mortality worldwide. Despite the availability, since the early 1980s, of a 23-valent pneumococcal polysaccharide vaccine (PP V23), its recommendation and increased use in the last decades, and the indirect benefits against invasive pneumococcal diseases following the pediatric immunization strategies with the 7-valent pneumococcal conjugate vaccine (PCV7), pneumoccal diseases, particularly Community Acquired Pneumonia (CAP), still remain a substantial burden among older adults in Western countries. The recent availability on the market of a second generation of pneumococcal conjugate vaccines, with an enlarged spectrum of protection against some serotypes not included in the PCV7 (i.e., the 13-valent pneumococcal conjugate vaccine--PCV13), opens new interesting perspectives for improving the control of this significant health-care issue among the entire population. The most interesting and up-dated epidemiological data regarding the impact of SP in adults and the elderly in Western countries, together with the available evidence concerning the efficacy and effectiveness of the PPV23 in the same population, are reported and discussed below.
Kuhlmann, Alexander; von der Schulenburg, J-Matthias Graf
In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.
Nguyen, MTT; Lindegaard, H.; Hendricks, O.
the survey during scheduled follow-up visits. The questionnaire included questions concerning previous influenza and pneumococcal vaccine uptake, attitudes about vaccination, and socio-demographic factors. Factors associated with recalled vaccine uptake were assessed by multivariate logistic regression....... Results: A total of 192 RA patients completed the survey, 134 (70%) of whom were women and 90 (47%) were aged ≥ 65 years. Sixty-seven patients (35%) received conventional disease-modifying anti-rheumatic drugs (cDMARDs) and 125 (65%) combination therapy with biological disease-modifying anti...
Frederiksen, B.; Specht, L.; Henrichsen, J.
Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in antib......Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase...
McCarthy, E M
Patients with inflammatory arthritis are at increased risk of vaccine preventable infections. This risk is increased by immunomodulatory therapies. Vaccination for influenza and pneumococcal disease reduces the risk. Severe cases of varicella infection have occurred in patients on biologic therapies. We sought to identify vaccination rates for commonly acquired infections and to ascertain varicella immune status in patients with inflammatory arthritis. 100 patients with inflammatory arthritis were administered a standardised questionnaire. Data collected included age, diagnosis, vaccination history, history of varicella, treatment and the presence of other indications for vaccination. 58 patients (58%) had not received the influenza vaccine in the past year. Only 19 patients (19%) had ever received pneumococcal vaccine. Anti TNF use did not predict vaccination (p = .46). An increasing number of co morbid conditions predicted both pneumococcal (p < 0.003) and influenza vaccine (p < 0.03) administration. Nineteen patients (19%) gave no history of varicella infection, none having had varicella titres checked pre treatment. Immunisation rates in patients with inflammatory arthritis on immunosuppressive therapies are low. Immunisation schedules should be available for each patient during rheumatology and general practice consultations.
García-Vera, César; Ruiz Andrés, María Ángeles; Arana Navarro, Teresa; Moneo Hernández, Isabel; Castillo Laita, José Antonio; Macipe Costa, Rosa; Revillo Pinilla, María José
To determine the characteristics influencing pneumococcal serotype colonization in healthy pre-school aged children, the distribution of serotypes and their antimicrobial susceptibility, after the introduction of pneumococcal 7-valent conjugate vaccine (VNC-7 v). SUJETOS AND METHODS: Nasopharyngeal samples were collected from children under 6 years of age attending well-child examinations in the province of Zaragoza (Spain). Logistic regression was used to study different variables related to the status of the carriers. Of the 371 children studied 30.7% were found to be carriers. With a vaccine coverage rate of 66%, factors related with presence of pneumococcal carriage were found to be the number of siblings (OR 1.44; CI 95% 1.05-1.97 for each sibling), attending a school or child day care centre (OR 3.99; CI 95% 2.00-7.96) and suffering from a minor upper respiratory tract infection (URTI) (OR 1.72; CI 95% 1.02-2.90). Only 8.7% corresponded to VNC-7 v serotypes. The most common non VNC-7 v serotypes isolated were 19A, 6A, 15B, 11, and 15A. Significantly greater resistance was detected among VNC-7 v serotypes. Children in the setting of this study carried pneumococci more commonly when they have siblings, attend school or day care, or suffer from minor URTI. In the VNC-7 v vaccine era, VNC-7 v serotypes have become rare occurrences (8.7%) and emerging serotypes present better susceptibility to antibiotics. Copyright © 2010 Elsevier España, S.L. All rights reserved.
Wysocki, Jacek; Brzostek, Jerzy; Szymański, Henryk; Tetiurka, Bogusław; Toporowska-Kowalska, Ewa; Wasowska-Królikowska, Krystyna; Sarkozy, Denise A; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A
Streptococcus pneumoniae infections are a major cause of morbidity and mortality in children vaccine (PCV13) has been developed and approved in many countries worldwide. Assess the safety and immunogenicity of PCV13 in healthy older infants and children naïve to previous pneumococcal vaccination. This was a phase 3, open-label, multicenter study conducted in Polish children (N=354) who were vaccinated according to 3 age-appropriate catch-up schedules: Group 1 (aged 7 to vaccine doses only; and Group 3 (aged 24 to vaccine, was determined for each vaccine serotype. In addition, antipolysaccharide immunoglobulin (Ig) G geometric mean concentrations (GMCs) were calculated. Safety assessments included systemic and local reactions, and adverse events. The proportion of immunological responders was ≥88% across groups for all serotypes. Antipolysaccharide IgG GMCs were generally similar across groups. Each schedule elicited immune response levels against all 13 serotypes comparable to or greater than levels previously reported in infants after a 3-dose series. The 3 catch-up schedules had similar tolerability and safety profiles; a trend was present towards greater local tenderness with increasing age and subsequent dose administration. Immunological responses and safety results support the use of PCV13 for catch-up schedules in older infants and children naïve to pneumococcal vaccination. Copyright © 2015. Published by Elsevier Ltd.
de Cellès, Matthieu Domenech; Pons-Salort, Margarita; Varon, Emmanuelle; Vibet, Marie-Anne; Ligier, Caroline; Letort, Véronique; Opatowski, Lulla; Guillemot, Didier
Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.
Michaelidis, Constantinos I.; Zimmerman, Richard K.; Nowalk, Mary Patricia; Smith, Kenneth J.
Objective Invasive pneumococcal disease is a major cause of preventable morbidity and mortality in the United States, particularly among the elderly (>65 years). There are large racial disparities in pneumococcal vaccination rates in this population. Here, we estimate the cost-effectiveness of a hypothetical national vaccination intervention program designed to eliminate racial disparities in pneumococcal vaccination in the elderly. Methods In an exploratory analysis, a Markov decision-analysis model was developed, taking a societal perspective and assuming a 1-year cycle length, 10-year vaccination program duration, and lifetime time horizon. In the base-case analysis, it was conservatively assumed that vaccination program promotion costs were $10 per targeted minority elder per year, regardless of prior vaccination status and resulted in the elderly African American and Hispanic pneumococcal vaccination rate matching the elderly Caucasian vaccination rate (65%) in year 10 of the program. Results The incremental cost-effectiveness of the vaccination program relative to no program was $45,161 per quality-adjusted life-year gained in the base-case analysis. In probabilistic sensitivity analyses, the likelihood of the vaccination program being cost-effective at willingness-to-pay thresholds of $50,000 and $100,000 per quality-adjusted life-year gained was 64% and 100%, respectively. Conclusions In a conservative analysis biased against the vaccination program, a national vaccination intervention program to ameliorate racial disparities in pneumococcal vaccination would be cost-effective. PMID:23538183
Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond
Abstract Background PCV13 replaced 7-valent pneumococcal conjugate vaccine in the routine infant immunization schedule in Mexico since 2011. The use of PCV13 has reduced pneumococcal disease incidence for vaccine serotypes, particularly 19A, which emerged following PCV7 use. The 10-valent vaccine (PCV10) contains the same serotypes as PCV13 with the exception of serotypes 3, 19A and 6A but also has different conjugated proteins for the common serotypes. This study evaluated the potential heal...
Olayinka, Folake; Ewald, Leah; Steinglass, Robert
The number of vaccines available to low-income countries has increased dramatically over the last decade. Overall infant immunization coverage in the WHO African region has stagnated in the past few years while countries' ability to maintain high immunization coverage rates following introduction of new vaccines has been uneven. This case study examines post-introduction coverage among African countries that introduced PCV between 2008 and 2013 and the factors affecting Pneumococcal Conjugate Vaccine (PCV) introduction. Nearly one-third of countries did not achieve 80% infant PCV3 coverage by two years post-introduction and 58% of countries experienced a decline in coverage between post introduction years two and four. Major factors affecting coverage rates included introduction without adequate preparation, insufficient supply chain capacity and management, poor communication between organizations and with the public, and data collection systems that were insufficient to meet information needs. Deliberately addressing these issues as well as longstanding weaknesses during new vaccine introduction can strengthen the immunization and broader health system. Further study is required to identify and address factors that affect maintenance of high coverage following introduction of new vaccines in the African region. Immunization with PCV is one of the most important interventions protecting against pneumonia, the second leading cause of death for children under five globally.
Daniels, Nicholas A; Gildengorin, Ginny; Nguyen, Tung T; Liao, Youlian; Luong, Thien-Nhien; McPhee, Stephen J
Vaccination data for Asian Americans are comparable to those for whites, possibly because they are reported in aggregate rather than for subgroups. We compared influenza and pneumococcal vaccination rates among eligible Asian Americans and white Americans, and for Vietnamese Americans as a subgroup, and assessed factors associated with these vaccinations. Cross-sectional study of data collected from three ethnic groups over 4 years by telephone survey. Data were weighted for selection probability and population estimates and analyzed by multivariate logistic regression. Vietnamese Americans had a higher rate of influenza vaccination (61%) than Asian Americans (45%) and white Americans (52%), and lower rate of pneumococcal vaccination (41%) than Asian Americans (56%), both lower than white Americans (67%). When analyzed as a subgroup, Vietnamese Americans had a higher influenza vaccination rate, but a lower pneumococcal vaccination rate, compared to Asian Americans and white Americans, which may indicate that health behaviors and outcomes can differ widely among Asian subgroups. Analyses of preventive care measures in Asian Americans should focus on subgroups to ensure accuracy and quality of assessments.
Medical Center. San pathogen is an even greater threat to some subpopulations in Diego, CA; Wyeth Lederle Vaccines: LT David Cute, MC USN, Erica...Butler JC. Tenover FC, Elliott JA, Facklam RR. Emergence of 43. Musher DM, Luchi MJ, Watson DA, Hamilton R, Baughn RE: Pneumococcal drug-resistant
Long, J.E.; Ring, C.; Bosch, J.A.; Eves, F.; Drayson, M.T.; Calver, R.; Say, V.; Allen, D.; Burns, V.E.
Objective: To assess whether a life-style physical activity intervention improved antibody response to a pneumococcal vaccination in sedentary middle-aged women. Methods: Eighty-nine sedentary women completed a 16-week exercise (physical activity consultation, pedometer, telephone/e-mail prompts; n
Gefenaite, Giedre; Bijlsma, Maarten J.; Bos, Jens; Hak, Eelko
Background: Streptococcus pneumoniae is responsible for a significant amount of respiratory infections and acute otitis media (AOM) and use of antibiotics in children. In June 2006 a four-dose 7-valent pneumococcal vaccination campaign (PVC) was introduced in the Netherlands; 94% of children born
Constenla, Dagna O
To evaluate the economic impact of vaccination with the pneumococcal 7-valent conjugate vaccine (PCV7) in Brazil, Chile, and Uruguay. A decision analytic model was constructed to compare pneumococcal vaccination of children 0-5 years old with no vaccination in Brazil, Chile, and Uruguay. Costs and health outcomes were analyzed from the societal perspective. Vaccine, demographic, epidemiologic, and cost data were incorporated into this economic analysis. At the rate of diphtheria-tetanus-pertussis (DTP) vaccine coverage and a vaccine price of US$ 53 per dose, PCV7 was projected to prevent 23 474 deaths per year in children under 5 years old in the three countries studied, thus averting 884,841 disability-adjusted life years (DALYs) yearly. To vaccinate the entire birth cohort of the three countries, total vaccine costs would be US$ 613.9 million. At US$ 53 per dose, the cost per DALY averted from a societal perspective would range from US$ 664 (Brazil) to US$ 2019 (Chile). At a cost of US$ 10 per dose, vaccine cost is lower than the overall cost of illness averted (US$ 125,050,497 versus US$ 153,965,333), making it cost effective and cost-saving. The results of this study demonstrate that the incorporation of PCV7 vaccine at US$ 53 per dose confers health benefits at extra costs. It is unclear whether vaccinatfon at the current price is affordable to these countries.
Pelton, Stephen I; Dagan, Ron; Gaines, Beverly M; Klugman, Keith P; Laufer, Dagna; O'Brien, Katherine; Schmitt, Heinz J
Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children. The emergence of antibiotic-resistant strains has increased interest in prevention through immunization. Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7. This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines. The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.
Fletcher, Mark A.; Fritzell, Bernard
Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486
van Hoek, Albert Jan; Choi, Yoon Hong; Trotter, Caroline; Miller, Elizabeth; Jit, Mark
In the immunisation schedule in England and Wales, the 7-valent pneumococcal conjugate vaccine (PCV-7) was replaced by the 13-valent vaccine (PCV-13) in April 2010 after having been used since September 2006. The introduction of PCV-7 was informed by a cost effectiveness analysis using an infectious disease model which projected herd immunity and serotype replacement effects based on the post-vaccine experience in the United States at that time. To investigate the cost effectiveness of the introduction of PCV-13. Invasive disease incidence following vaccination was projected from a dynamic infectious disease model, and combined with serotype specific disease outcomes obtained from a large hospital dataset linked to laboratory confirmation of invasive pneumococcal disease. The economic impact of replacing PCV-7 with PCV-13 was compared to stopping the use of pneumococcal conjugate vaccination altogether. Discontinuing PCV-7 would lead to a projected increase in invasive pneumococcal disease, costs and loss of quality of life compared to the introduction of PCV-13. However under base case assumptions (assuming no impact on non-invasive disease, maximal competition between vaccine and non-vaccine types, time horizon of 30 years, vaccine price of £49.60 a dose+£7.50 administration costs and discounting of costs and benefits at 3.5%) the introduction of PCV-13 is only borderline cost effective compared to a scenario of discontinuing of PCV-7. The intervention becomes more cost-effective when projected impact of non-invasive disease is included or the discount factor for benefits is reduced to 1.5%. To our knowledge this is the first evaluation of a transition from PCV-7 to PCV-13 based on a dynamic model. The cost-effectiveness of such a policy change depends on a number of crucial assumptions for which evidence is limited, particularly the impact of PCV-13 on non-invasive disease. Copyright © 2012 Elsevier Ltd. All rights reserved.
M. V. Fedoseenko
Full Text Available Compulsory use of the 7-valent pneumococcal conjugate vaccine in the framework of national pediatric immunization schedules of the developed countries resulted in significant decrease in the prevalence of the pneumococcal infections induced by the vaccinal serotypes. However, a growth in prevalence of the pneumonia and acute otitis media caused by non-vaccinal strains has also been observed. This required introduction of a new 13-valent pneumococcal conjugate vaccine with a wider range of pneumococcal population coverage. The experience of application accumulated in various countries (2010 onwards and results of the authors’ observations indicate high safety of the 13-valent pneumococcal conjugate vaccine for both healthy under-5 children and patients with various medical issues. The article presents results of the 13-valent pneumococcal conjugate vaccination tolerance assessment. The study involved 110 children from 2 months to 5 years of age. In most cases immunization concurred with other pediatric vaccines. The incidence of local reactions in vaccinated children did not exceed 33%, of generalized reactions – 11%. The authors observed a comparable incidence of side reactions in both virtually healthy children and children with various medical issues.
M. Teresa Valenzuela B.
Full Text Available S. pneumoniae is a significant cause of community-acquired pneumonia in the elderly, and accounts for the majority of the pneumonia deaths among the elderly. We conducted this randomized double-blind study to evaluate the immune response to a 23-valent pneumococcal polysaccharide vaccine and the persistence of antibodies two years after the vaccination in an elderly population in Santiago, Chile. A total of 118 elderly nursing home residents received either the pneumococcal or a tetanus control vaccine. Serum samples were taken at enrolment, at two months, and at two years post-vaccination. Pre-vaccination anti-pneumococcal antibody geometric mean concentrations (GMC were similar in both study groups, with increased levels of antibodies found only against serotype 14. The pneumococcal vaccine was highly immunogenic at 2 months, and titers remained high two years after the vaccination for the 10 serotypes studied in this elderly population. The results thus support the benefits of this pneumococcal vaccine in this elderly population who are at increased risk of invasive pneumococcal disease.
Azarian, Taj; Grant, Lindsay R; Arnold, Brian J; Hammitt, Laura L; Reid, Raymond; Santosham, Mathuram; Weatherholtz, Robert; Goklish, Novalene; Thompson, Claudette M; Bentley, Stephen D; O'Brien, Katherine L; Hanage, William P; Lipsitch, Marc
In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998-2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998-2000) than the preceding period (2006-2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal
Hammitt, Laura L.; Santosham, Mathuram; Goklish, Novalene; Thompson, Claudette M.; Bentley, Stephen D.; O’Brien, Katherine L.
In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998–2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998–2000) than the preceding period (2006–2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein
Giuseppe La Torre
Full Text Available Background The risk of getting influenza and pneumococcal disease is higher in cancer patients and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To asses flu and pneumococcal vaccinations efficacy, effectiveness and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in scientific literature about flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 23 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI = 6.2- 61% for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI = 23.2 – 63.3 % and 39.6 % (95% CI = 26%- 54.1% for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI = 19.7-51.2% for H1N1, 23% (95% CI = 16.6-31.5% for H3N2, 29% (95% CI = 21.3- 37% for B. Conclusion Despite low rate of response, flu and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines.
Long, Joanna E; Ring, Chris; Bosch, Jos A; Eves, Francis; Drayson, Mark T; Calver, Rebecca; Say, Vanessa; Allen, Daniel; Burns, Victoria E
To assess whether a life-style physical activity intervention improved antibody response to a pneumococcal vaccination in sedentary middle-aged women. Eighty-nine sedentary women completed a 16-week exercise (physical activity consultation, pedometer, telephone/e-mail prompts; n = 44) or control (advisory leaflet; n = 45) intervention. Pneumococcal vaccination was administered at 12 weeks, and antibody titers (11 of the 23 contained in the pneumococcal vaccine) were determined before vaccination and 4 weeks and 6 months later. Physical activity, aerobic fitness, body composition, and psychological factors were measured before and after the intervention. The intervention group displayed a greater increase in walking behavior (from mean [standard deviation] = 82.16 [90.90] to 251.87 [202.13]) compared with the control condition (111.67 [94.64] to 165.16 [117.22]; time by group interaction: F(1,68) = 11.25, p = .001, η(2) = 0.14). Quality of life also improved in the intervention group (from 19.37 [3.22] to 16.70 [4.29]) compared with the control condition (19.97 [4.22] to 19.48 [5.37]; time by group interaction: F(1,66) = 4.44, p = .039, η(2) = 0.06). However, no significant effects of the intervention on antibody response were found (time by group η(2) for each of the 11 pneumococcal strains ranged from 0.001 to 0.018; p values all >.264). Participation in a life-style physical activity intervention increased subjective and objective physical activity levels and quality of life but did not affect antibody response to pneumococcal vaccination.
Maurer, Kristin A; Chen, Huey-Fen; Wagner, Abram L; Hegde, Sonia T; Patel, Tejasi; Boulton, Matthew L; Hutton, David W
Although China has a high burden of pneumococcal disease among young children, the government does not administer publicly-funded pneumococcal conjugate vaccines (PCV) through its Expanded Program on Immunization (EPI). We evaluated the cost-effectiveness of publicly-funded PCV-7, PCV-10, and PCV-13 vaccination programs for infants in China. Using a Markov model, we simulated a cohort of 16 million Chinese infants to estimate the impact of PCV-7, PCV-10, and PCV-13 vaccination programs from a societal perspective. We extrapolated health states to estimate the effects of the programs over the course of a lifetime of 75years. Parameters in the model were derived from a review of the literature. We found that PCV-7, PCV-10, and PCV-13 vaccination programs would be cost-effective compared to no vaccination. However, PCV-13 had the lowest incremental cost-effectiveness ratio ($11,464/QALY vs $16,664/QALY for PCV-10 and $18,224/QALY for PCV-7) due to a reduction in overall costs. Our sensitivity analysis revealed that the incremental cost-effectiveness ratios were most sensitive to the utility of acute otitis media, the cost of PCV-13, and the incidence of pneumonia and acute otitis media. The Chinese government should take steps to reduce the burden of pneumococcal diseases among young children through the inclusion of a pneumococcal conjugate vaccine in its EPI. Although all vaccinations would be cost-effective, PCV-13 would save more costs to the healthcare system and would be the preferred strategy. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Gyhrs, A; Pedersen, B K; Bygbjerg, I
(1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined...... dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....
Full Text Available Abstract Background Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7. We compare the cost effectiveness of a 13-valent PCV (PCV-13 and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV with that of PCV-7 in Turkey. Methods A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population Results PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Conclusion Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children.
Licciardi, Paul V; Toh, Zheng Quan; Clutterbuck, Elizabeth A; Balloch, Anne; Marimla, Rachel A; Tikkanen, Leena; Lamb, Karen E; Bright, Kathryn J; Rabuatoka, Uraia; Tikoduadua, Lisi; Boelsen, Laura K; Dunne, Eileen M; Satzke, Catherine; Cheung, Yin Bun; Pollard, Andrew J; Russell, Fiona M; Mulholland, Edward K
A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Maria Leonor S Oliveira
Full Text Available Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines. Efficient immune responses directed to PspA in animal models have already been described. Nevertheless, few low cost adjuvants for a subunit pneumococcal vaccine have been proposed to date. Here, we have tested the adjuvant properties of the whole cell Bordetella pertussis vaccine (wP that is currently part of the DTP (diphtheria-tetanus-pertussis vaccine administrated to children in several countries, as an adjuvant to PspA. Nasal immunization of BALB/c mice with a combination of PspA5 and wP or wP(low--a new generation vaccine that contains low levels of B. pertussis LPS--conferred protection against a respiratory lethal challenge with S. pneumoniae. Both PspA5-wP and PspA5-wP(low vaccines induced high levels of systemic and mucosal antibodies against PspA5, with similar profile, indicating no essential requirement for B. pertussis LPS in the adjuvant properties of wP. Accordingly, nasal immunization of C3H/HeJ mice with PspA5-wP conferred protection against the pneumococcal challenge, thus ruling out a role for TLR4 responses in the adjuvant activity and the protection mechanisms triggered by the vaccines. The high levels of anti-PspA5 antibodies correlated with increased cross-reactivity against PspAs from different clades and also reflected in cross-protection. In addition, passive immunization experiments indicated that antibodies played an important role in protection in this model. Finally, subcutaneous immunization with a combination of PspA5 with DTP(low protected mice against challenge with two
Albert Jan van Hoek
Full Text Available Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13 among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7 since 2006 and PCV13 since 2010, as well as a 23-valent pneumococcal polysaccharide (PPV23 vaccination programme targeting clinical risk-groups and those ≥65 years.A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results.The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP, and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust.Vaccinating
Daniel R Feikin
Full Text Available BACKGROUND: Vaccine-serotype (VT invasive pneumococcal disease (IPD rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7 into national immunization programs. Increases in non-vaccine-serotype (NVT IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65 and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68. Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10, while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71. Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]. CONCLUSIONS: Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not
Winthrop, Kevin L; Silverfield, Joel; Racewicz, Arthur; Neal, Jeffrey; Lee, Eun Bong; Hrycaj, Pawel; Gomez-Reino, Juan; Soma, Koshika; Mebus, Charles; Wilkinson, Bethanie; Hodge, Jennifer; Fan, Haiyun; Wang, Tao; Bingham, Clifton O
To evaluate tofacitinib's effect upon pneumococcal and influenza vaccine immunogenicity. We conducted two studies in patients with rheumatoid arthritis using the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) and the 2011-2012 trivalent influenza vaccine. In study A, tofacitinib-naive patients were randomised to tofacitinib 10 mg twice daily or placebo, stratified by background methotrexate and vaccinated 4 weeks later. In study B, patients already receiving tofacitinib 10 mg twice daily (with or without methotrexate) were randomised into two groups: those continuing ('continuous') or interrupting ('withdrawn') tofacitinib for 2 weeks, and then vaccinated 1 week after randomisation. In both studies, titres were measured 35 days after vaccination. Primary endpoints were the proportion of patients achieving a satisfactory response to pneumococcus (twofold or more titre increase against six or more of 12 pneumococcal serotypes) and influenza (fourfold or more titre increase against two or more of three influenza antigens). In study A (N=200), fewer tofacitinib patients (45.1%) developed satisfactory pneumococcal responses versus placebo (68.4%), and pneumococcal titres were lower with tofacitinib (particularly with methotrexate). Similar proportions of tofacitinib-treated and placebo-treated patients developed satisfactory influenza responses (56.9% and 62.2%, respectively), although fewer tofacitinib patients (76.5%) developed protective influenza titres (≥1:40 in two or more of three antigens) versus placebo (91.8%). In study B (N=183), similar proportions of continuous and withdrawn patients had satisfactory responses to PPSV-23 (75.0% and 84.6%, respectively) and influenza (66.3% and 63.7%, respectively). Among patients starting tofacitinib, diminished responsiveness to PPSV-23, but not influenza, was observed, particularly in those taking concomitant methotrexate. Among existing tofacitinib users, temporary drug discontinuation had limited
... pneumococcal disease kills one in every four to five people over the age of 65 who gets it. ... A second PPSV23 vaccine is recommended for these persons five years after the first PPSV23. CDC recommends only ...
Sinha, Anushua; Levine, Orin; Knoll, Maria D; Muhib, Farzana; Lieu, Tracy A
Routine vaccination of infants against Streptococcus pneumoniae (pneumococcus) needs substantial investment by governments and charitable organisations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate these data into an economic analysis of pneumococcal vaccination of infants in countries eligible for financial support from the Global Alliance for Vaccines & Immunization (GAVI). We constructed a decision analysis model to compare pneumococcal vaccination of infants aged 6, 10, and 14 weeks with no vaccination in the 72 countries that were eligible as of 2005. We used published and unpublished data to estimate child mortality, effectiveness of pneumococcal conjugate vaccine, and immunisation rates. Pneumococcal vaccination at the rate of diptheria-tetanus-pertussis vaccine coverage was projected to prevent 262,000 deaths per year (7%) in children aged 3-29 months in the 72 developing countries studied, thus averting 8.34 million disability-adjusted life years (DALYs) yearly. If every child could be reached, up to 407,000 deaths per year would be prevented. At a vaccine cost of International 5 dollars per dose, vaccination would have a net cost of 838 million dollars, a cost of 100 dollars per DALY averted. Vaccination at this price was projected to be highly cost-effective in 68 of 72 countries when each country's per head gross domestic product per DALY averted was used as a benchmark. At a vaccine cost of between 1 dollar and 5 dollars per dose, purchase and accelerated uptake of pneumococcal vaccine in the world's poorest countries is projected to substantially reduce childhood mortality and to be highly cost-effective.
Giglio, Norberto D; Cane, Alejandro D; Micone, Paula; Gentile, Angela
Due to the region's own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial. To compare projected economic costs and health benefits associated with pneumococcal conjugate heptavalent vaccine as a routine immunization in healthy children in Argentina. A decision analytic model of Markov simulated lifetime evolution of a birth cohort (n 696,451) was developed and compared costs and health benefits of pneumococcal disease in the presence and absence of vaccination. Cost per life year (LY) gained, reduce in diseases burden and costs of vaccination. From the society's perspective, the incremental cost per LY gained was US$ 5599.42 and the purchase of the 4 doses of vaccine for the entire cohort with a cost of US$ 26.5 dose requires an investment of US$ 73,823,806.00. The model estimated that vaccination reduce the number of death by 159 cases of meningitis, 756 cases of bacteriemias 4594 cases of pneumonias about 84,769 cases of otitis media and 20 meningitis sequelae. The value of the cost per LY gained was considerably modified by the variation in the cost of the vaccine dose, efficacy/effectiveness of the vaccine for pneumonia the mortality from pneumonia and herd immunity. Our analysis predicted that routine vaccination of healthy infants <2 years could prevent an important number of pneumococcal infectious and reduce related mortality and morbidity. This strategic could be highly cost-effective in Argentina. Copyright 2010 Elsevier Ltd. All rights reserved.
Strutton David R
Full Text Available Abstract Background Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1 outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. Methods A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7 on pneumococcal disease incidence and mortality during a typical influenza season (13/100 and a severe influenza pandemic (30/100. Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd protection of non-vaccinated persons. Results The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd protection in the unvaccinated. Conclusions PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.
Rubin, Jaime L; McGarry, Lisa J; Klugman, Keith P; Strutton, David R; Gilmore, Kristen E; Weinstein, Milton C
Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.
Aljunid, Syed; Abuduxike, Gulifeiya; Ahmed, Zafar; Sulong, Saperi; Nur, Amrizal Muhd; Goh, Adrian
Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7. A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population. At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million). Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million) to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261) per life year gained. PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261). This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922).
Moreira, Marta; Cintra, Otavio; Harriague, Julie; Hausdorff, William P; Hoet, Bernard
Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.
Looijmans-van den Akker, I; van den Heuvel, P.M.; Verheij, Th J M; van Delden, J J M; van Essen, G A; Hak, E
OBJECTIVE: Smoking increases the risk for influenza and pneumococcal disease, but vaccination uptake is lower among smokers than non-smokers. We therefore aimed to determine reasons for not complying with vaccination among smokers and non-smokers. METHOD: In 2005 a self-administered questionnaire
Kuipers, Kirsten; Van Selm, Saskia; van Opzeeland, Fred; Langereis, Jeroen D.; Verhagen, Lilly M.; Diavatopoulos, Dimitri A.; De Jonge, Marien I.
Vaccination has been one of the most successful strategies to reduce morbidity and mortality caused by respiratory infections. Recent evidence suggests that differences in the host genetic background and environmental factors may contribute to heterogeneity in the immune response to vaccination.
Jennifer R Verani
Full Text Available Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful for evaluating pneumococcal conjugate vaccine (PCV impact. We studied pre-PCV pneumococcal carriage among HIV-infected and -uninfected children in Mozambique. Between October 2012 and March 2013, we enrolled HIV-infected children age <5 years presenting for routine care at seven HIV clinics in 3 sites, including Maputo (urban-south, Nampula (urban-north, and Manhiça (rural-south. We also enrolled a random sample of HIV-uninfected children <5 years old from a demographic surveillance site in Manhiça. A single nasopharyngeal swab was obtained and cultured following enrichment in Todd Hewitt broth with yeast extract and rabbit serum. Pneumococcal isolates were serotyped by Quellung reaction and multiplex polymerase chain reaction. Factors associated with pneumococcal carriage were examined using logistic regression. Overall pneumococcal carriage prevalence was 80.5% (585/727, with similar prevalences among HIV-infected (81.5%, 339/416 and HIV-uninfected (79.1%, 246/311 children, and across age strata. Among HIV-infected, after adjusting for recent antibiotic use and hospitalization, there was no significant association between study site and colonization: Maputo (74.8%, 92/123, Nampula (83.7%, 82/98, Manhiça (84.6%, 165/195. Among HIV-uninfected, report of having been born to an HIV-infected mother was not associated with colonization. Among 601 pneumococcal isolates from 585 children, serotypes 19F (13.5%, 23F (13.1%, 6A (9.2%, 6B (6.2% and 19A (5.2% were most common. The proportion of serotypes included in the 10- and 13-valent vaccines was 44.9% and 61.7%, respectively, with no significant differences by HIV status or age group. Overall 36.9% (n = 268 of children were colonized with a PCV10 serotype and 49.7% (n = 361 with a PCV13 serotype. Pneumococcal carriage was common, with little variation by geographic region, age, or HIV status. PCV10 was introduced in
Kondo, Kyoko; Suzuki, Kanzo; Washio, Masakazu; Ohfuji, Satoko; Fukushima, Wakaba; Maeda, Akiko; Hirota, Yoshio
We conducted a case-control study to elucidate associations between pneumonia in elderly individuals and 23-valent pneumococcal polysaccharide vaccine (PPSV23) and seasonal influenza vaccine (influenza vaccine). Here, we examined selection of controls in our study using an analytic epidemiology approach. The study period was from October 1, 2009 through September 30, 2014. Cases comprised ≥65-year-old patients newly diagnosed with pneumonia. For every case with pneumonia, two patients with other diseases (one respiratory medicine, one non-respiratory medicine) who were sex-, age-, visit date- and visit hospital-matched were selected as controls. Odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for pneumonia were calculated using conditional logistic regression model. Similar analyses were also conducted based on the clinical department of controls. Analysis was conducted in 234 cases and 438 controls. Effectiveness of pneumococcal vaccination or influenza vaccination against pneumonia was not detected. Proportions of either vaccination in controls were greater among respiratory medicine (pneumococcal vaccine, 38%; influenza vaccine, 55%) than among non-respiratory medicine (23%; 48%). Analysis using controls restricted to respiratory medicine showed marginally significant effectiveness of pneumococcal vaccination (OR, 0.59; 95%CI, 0.34-1.03; P=0.064) and influenza vaccination (0.64; 0.40-1.04; 0.072). However, this effectiveness might have been overestimated by selection bias of controls, as pneumonia cases are not necessarily respiratory medicine patients. In the analysis using controls restricted to non-respiratory medicine, OR of pneumococcal vaccination for pneumonia was close to 1, presumably because the proportion of pneumococcal vaccination was higher in cases than in controls. Because pneumococcal vaccine was not routinely administered during the study period, differences in recommendations of vaccination by physician in different
Taylor, Sylvia; Marchisio, Paola; Vergison, Anne; Harriague, Julie; Hausdorff, William P.; Haggard, Mark
Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%–9% in randomized trials and 17%–23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3–5 years before 7vCRM introduction (mean change, −15%; range, +14% to −24%) and continued to decline afterward (mean, −19%; range, +7% to −48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM. PMID:22423134
Maricruz Gutiérrez Brito
Full Text Available OBJECTIVE: To assess the safety and immune responses induced by a 13-valent pneumococcal conjugate vaccine (PCV13 after immunization of infants in Mexico. METHODS: PCV13 was given with other routine childhood vaccinations to 225 infants in Mexico at ages 2, 4, 6, and 12 months. RESULTS: The proportions of subjects achieving immunoglobulin G (IgG concentrations ≥0.35 µg/mL after the infant series and toddler dose were ≥93.1% and ≥96.7%, respectively, for all 13 serotypes. The serotype-specific pneumococcal IgG geometric mean concentrations after the infant series and toddler dose ranged from 1.18 to 9.13 µg/mL and from 1.62 to 15.41 µg/mL, respectively. The most common local reaction and systemic event after each dose were tenderness and irritability, respectively. Most fever was mild; no fever >40.0°C (i.e., severe was reported. One subject withdrew because of Kawasaki disease 5 days after the first dose of vaccines, but this condition was not considered related to PCV13. CONCLUSIONS: Overall, PCV13 administered with routine pediatric vaccines was immunogenic and safe in healthy infants in Mexico.
Sundaram, Neisha; Chen, Cynthia; Yoong, Joanne; Luvsan, Munkh-Erdene; Fox, Kimberley; Sarankhuu, Amarzaya; La Vincente, Sophie; Jit, Mark
The Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia. The incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3+0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance's advance market commitment tail price. The ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025. Introducing PCV13 as part of Mongolia's national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains
Pumarola, Felix; Salamanca de la Cueva, Ignacio; Sistiaga-Hernando, Alessandra; García-Corbeira, Pilar; Moraga-Llop, Fernando A; Cardelús, Sara; McCoig, Cynthia; Gómez Martínez, Justo Ramón; Rosell Ferrer, Rosa; Iniesta Turpin, Jesús; Devadiga, Raghavendra
Acute otitis media (AOM) is common in children aged <3 years. A pneumococcal conjugate vaccine (PCV) (PCV7; Prevenar, Pfizer/Wyeth, USA) has been available in Spain since 2001, which has a coverage rate of 50-60% in children aged <5 years. Children aged ≥3 to 36 months with AOM confirmed by an ear-nose-throat specialist were enrolled at seven centers in Spain (February 2009-May 2012) (GSK study identifier: 111425). Middle-ear-fluid samples were collected by tympanocentesis or spontaneous otorrhea and cultured for bacterial identification. Culture-negative samples were further analyzed using polymerase chain reaction (PCR). Of 125 confirmed AOM episodes in 124 children, 117 were analyzed (median age: 17 months (range: 3-35); eight AOM episodes were excluded from analyses. Overall, 69% (81/117) episodes were combined culture- and PCR-positive for ≥1 bacterial pathogen; 44% (52/117) and 39% (46/117) were positive for Haemophilus influenzae (Hi) and Streptococcus pneumoniae (Spn), respectively. 77 of 117 episodes were cultured for ≥1 bacteria, of which 63 were culture-positive; most commonly Spn (24/77; 31%) and Hi (32/77; 42%). PCR on culture-negative episodes identified 48% Hi- and 55% Spn-positive episodes. The most common Spn serotype was 19F (4/24; 17%) followed by 19A (3/24; 13%); all Hi-positive episodes were non-typeable (NTHi). 81/117 AOM episodes (69%) occurred in children who had received ≥1 pneumococcal vaccine dose. NTHi and Spn were the main etiological agents for AOM in Spain. Impact of pneumococcal vaccination on AOM requires further evaluation in Spain, after higher vaccination coverage rate is reached. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Dagna O. Constenla
Full Text Available OBJECTIVE:A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV programs in Ecuador, Honduras, and Paraguay from the societal perspective. METHODS: Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. RESULTS: Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY averted for the 10-valent PCV (PCV10 and the 13-valet PCV (PCV13 ranged from US$ 796 (Honduras to US$ 1 340 (Ecuador and from US$ 691 (Honduras to US$ 1 166 (Ecuador respectively. At a reduced price (US$ 7 per dose, the cost per DALY averted ranged from US$ 327 (Honduras to US$ 528 (Ecuador and from US$ 281 (Honduras to US$ 456 (Ecuador for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. CONCLUSIONS: The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints.
Constenla, Dagna O
A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV) programs in Ecuador, Honduras, and Paraguay from the societal perspective. Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY) averted for the 10-valent PCV (PCV10) and the 13-valet PCV (PCV13) ranged from US$ 796 (Honduras) to US$ 1 340 (Ecuador) and from US$ 691 (Honduras) to US$ 1 166 (Ecuador) respectively. At a reduced price (US$ 7 per dose), the cost per DALY averted ranged from US$ 327 (Honduras) to US$ 528 (Ecuador) and from US$ 281 (Honduras) to US$ 456 (Ecuador) for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints.
Çiftci, Fatma; Şen, Elif; Demir, Nalan; Çiftci, Orçun; Erol, Serhat; Kayacan, Oya
Vaccination of healthcare personnel (HCP) is an effective measure for preventing the spread of influenza among at-risk patients. This study was conducted to determine influenza vaccination rates and activities among HCP working at a tertiary healthcare setting. This study included 470 HCP (85 physicians, 134 nurses, 53 healthcare assistants, 44 paramedics, 47 medical secretaries, and 107 auxillary staff members) working at the emergency, cardiology, chest diseases, and internal medicine departments with the largest volume of patients with vaccination indication of two large university hospitals with similar medical practices and work environment. Each participant completed an anonymous questionnaire form. A total of 470 HCP participated in the survey. The compliance rate of the HCP to participate in the survey was 93.6%. Of these, 26.7% had been vaccinated against influenza. Vaccination in the survey year was significantly associated with having regular influenza vaccinations (OR 48.66; 95% CI:[25.09-94.369]; P<.01); having an educational level of college or higher (OR 2.07; 95% CI:[1.03-4.15]; P<.05); being a physician (OR 4.25; 95% CI:[1.28-14.07]; P< .05); and a professional experience of more than 5 years (OR 2.02; 95%CI:[1.13-5.62]; P< .05). Physicians recommended and prescribed the influenza vaccine significantly more frequently than the pneumococcal vaccine (37.6% vs 30.6%, P = .03, 25.9% vs 17.6%, P = .001, respectively). Among all HCP, the reasons for vaccination included having the opinion that the vaccine provides a partial protection against the infection (75.2%), reduces work force loss (48.8%), reduces the rates of death and severe conditions like pneumonia (43.2%), and reduces hospitalization (40.8%). The HCP had been vaccinated to protect family members (81.6%), people around (51.2%), herself/himself (47.2%), and patients (28%) fom infection. The reasons of not getting vaccinated against influenza among HCP included fear of vaccine's adverse
Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente
A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173. Copyright © 2014 Elsevier Ltd. All rights reserved.
van Westen, Els; Wijmenga-Monsuur, Alienke J; van Dijken, Harry H; van Gaans-van den Brink, Jacqueline A M; Kuipers, Betsy; Knol, Mirjam J; Berbers, Guy A M; Sanders, Elisabeth A M; Rots, Nynke Y; van Els, Cécile A C M
BACKGROUND: Both the 10- and 13-valent pneumococcal conjugate vaccines (PCV10 and PCV13) induce immunological memory against Streptococcus pneumoniae infections caused by vaccine serotypes. In addition to comparing serum antibody levels, we investigated frequencies of serotype-specific plasma cells
Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children : a randomized, double-blind, placebo-controlled trial
Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko
OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with
dos Santos, Silvia R; Passadore, Lilian F; Takagi, Elizabeth H; Fujii, Cristiane M; Yoshioka, Cristina R M; Gilio, Alfredo E; Martinez, Marina B
The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination
Che, Datian; Zhou, Hua; He, Jinchun; Wu, Bin
The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2 + 1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization.
Earnshaw Stephanie R
Full Text Available Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13 and 10-valent pneumococcal conjugate vaccine (PCV10 are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi. We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public
Ingels, Helene Andrea Sinclair
Streptococcus pneumoniae is still a leading cause of septicaemia, pneumonia and meningitis in young children world-wide with over half a million children dying annually from pneumococcal disease. Some children are prone to repeated episodes of invasive pneumococcal disease (IPD) because of an underlying predisposing disease. Recurrent IPD (rIPD) is a rarity and published reports on rIPD are limited by having few children included, selected groups of patients or short follow-up periods. Deficiencies in the innate or adaptive immune system have been described in children with rIPD, but the frequency of immunodeficiency among such patients is unknown. The aim of this PhD thesis was to examine paediatric cases of laboratory-confirmed rIPD, over a 33-year period in Denmark, to determine risk factors and study aspects of the immunological background for this problem in children. In October 2007, a seven-valent pneumococcal conjugate vaccine (PCV7) was implemented in the Danish infant immunization programme. An additional aim of the thesis was to examine the impact of vaccination on a population level, following the first three years of general PCV7 vaccination in Denmark. The thesis consists of three papers, which are all directly or indirectly based on data retrieved from the National Streptococcus Pneumoniae Registry. This registry is nationwide and dates back to 1938. The registry contains data from all laboratory-confirmed cases of IPD in Denmark and is continually updated for national surveillance. In Paper 1, we conducted a 33-year retrospective nationwide study of paediatric rIPD. By using data from the National Streptococcus Pneumoniae Registry combined with clinical data from hospital records, we could describe one of the largest known cohorts of children (n:59) with rIPD . We covered epidemiological, microbiological, and clinical features of this clinical entity. Of all children experiencing rIPD, 47% had a known predisposing underlying disease at the time of
Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial.
Nakashima, Kei; Aoshima, Masahiro; Ohfuji, Satoko; Yamawaki, Satoshi; Nemoto, Masahiro; Hasegawa, Shinya; Noma, Satoshi; Misawa, Masafumi; Hosokawa, Naoto; Yaegashi, Makito; Otsuka, Yoshihito
It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, -10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4-6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).
Kondo, Masahide; Yamamura, Mariko; Hoshi, Shu-Ling; Okubo, Ichiro
Vaccination programs often organize subsidies and public relations in order to obtain high uptake rates and coverage. However, effects of subsidies and public relations have not been studied well in the literature. In this study, the demand function of pneumococcal vaccination among the elderly in Japan is estimated, incorporating effects of public relations and subsidy. Using a data from a questionnaire survey sent to municipalities, the varying and constant elasticity models were applied to estimate the demand function. The response variable is the uptake rate. Explanatory variables are: subsidy supported shot price, operating years of the program, target population size for vaccination, shot location intensity, income and various public relations tools. The best model is selected by c-AIC, and varying and constant price elasticities are calculated from estimation results. The vaccine uptake rate and the shot price have a negative relation. From the results of varying price elasticity, the demand for vaccination is elastic at municipalities with a shot price higher than 3,708 JPY (35.7 USD). Effects of public relations on the uptake rate are not found. It can be suggested that municipalities with a shot price higher than 3,708 JPY (35.7 USD) could subsidize more and reduce price to increase the demand for vaccination. Effects of public relations are not confirmed in this study, probably due to measurement errors of variables used for public relations, and studies at micro level exploring individual's response to public relations would be required.
Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age ▿
Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray
The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all thr...
Wu, David Bin-Chia; Chaiyakunapruk, Nathorn; Chong, Huey-Yi; Beutels, Philippe
Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs ("PCV10" and "PCV13"). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch. This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006. We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies. Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study. A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer. Copyright © 2015 Elsevier
Tsuda, Yuko; Watanabe, Misuzu; Tanimoto, Yoshimi; Hayashida, Itsushi; Kusabiraki, Toshiyuki; Komiyama, Maki; Kono, Koichi
This study aimed to understand the current scenario of voluntary vaccination and the factors influencing its coverage among 18-month-old children of Takatsuki City, Japan. Based on 1167 parents responses, we found that voluntary vaccination coverage rates were low when compared with routine vaccination rates. The children who were not the first born of the family and who had young and poorly educated parents were less likely to receive voluntary vaccination. Japanese government-supported vaccines, such as Haemophilus influenzae type b and pneumococcal vaccine, had a higher coverage than the vaccines for which parents had to bear the entire vaccination cost. Furthermore, it was found that mass communication media and family pediatricians were effective means to disseminate voluntary vaccination-related information. We envisage that an active participation of medical professionals, easy access to vaccinations, and mass awareness programs will increase voluntary vaccination coverage in Takatsuki. © 2013 APJPH.
Pentakota, Sri Ram; Halperin, William
In 2002, federal regulations authorized the use of standing orders programs (SOPs) for promoting influenza and pneumococcal vaccination. In 2003, the New Jersey Hospital Association conducted a demonstration project illustrating the efficacy of SOPs, and the state health department informed healthcare facilities of their benefits. We describe the prevalence of reported use of SOPs in New Jersey hospitals in 2003 and 2005 and identify hospital characteristics associated with the use of SOPs. A survey was mailed to the directors of infection control at 117 New Jersey hospitals during the period from January to May 2005 (response rate, 90.6%). Data on hospital characteristics were obtained from hospital directories and online resources. The prevalence of use of SOPs for influenza vaccination was 50% (95% confidence interval [CI], 40.1%-59.9%) in 2003, and it increased to 78.3% (95% CI, 69.2%-85.7%) in 2005. The prevalence of SOP use for pneumococcal vaccination was similar. In 2005, the reported rate of use of SOPs for inpatients (influenza vaccination, 76.4%; pneumococcal vaccination, 75.5%) was significantly higher than that for outpatients (influenza vaccination, 9.4%; pneumococcal vaccination, 8.5%). Prevalence ratios for SOP use comparing acute care and non-acute care hospitals were 1.71 (95% CI, 1.2-2.5) for influenza vaccination SOPs and 1.8 for (95% CI, 1.2-2.7) pneumococcal vaccination SOPs. Acute care hospitals with a ratio of admissions to total beds greater than 36.7 reported greater use of SOPs for pneumococcal vaccination, compared with those that had a ratio of less than 36.7. The increase in the prevalence of reported use of SOPs among New Jersey hospitals in 2005, compared with 2003, was contemporaneous with SOP-related actions taken by the federal government, the state government, and the New Jersey Hospital Association. Opportunities persist for increased use of SOPs among non-acute care hospitals and for outpatients.
Janssen, Willemijn J M; Nierkens, Stefan; Sanders, Elisabeth A; Boes, Marianne; van Montfrans, Joris M
Paediatric patients with antibody deficiency may either be delayed in development of humoral immunity or may be persistently deficient in antibody production. To differentiate between these entities, we examined the 23-valent pneumococcal polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA
Jansen, Angelique G S C; Sanders, Elisabeth A M; Smulders, Sara; Hoes, Arno W; Hak, Eelko
In a randomized double-blind controlled trial, the safety was assessed of simultaneous administration of influenza and pneumococcal conjugate vaccines in children with previous physician-diagnosed respiratory tract infections. In total, 579 children aged 18-72 months were assigned to receive
Full Text Available Following the introduction of 7- and 13-pneumococcal conjugate vaccines (PCVs in Israel, we demonstrated that within Streptococcus pneumoniae (Sp positive middle ear cultures, obtained from young children with severe acute otitis media (AOM episodes, there were more penicillin-susceptible and less multi-drug resistant Sp isolates in PCV immunized children.
Warren, Joshua L.; Shioda, Kayoko; Kürüm, Esra
Background: Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used t...
Belongia Edward A
Full Text Available Abstract Background Pneumococcal polysaccharide vaccine (PPV is recommended for all adults 65 years of age and older and for younger adults with high-risk conditions. While data from national surveys provide information on the proportion of adults 65 years of age and older reporting ever receipt of PPV they do not collect more detailed information, such as age at vaccination or the total number of vaccinations received. In addition, there is relatively little information available on PPV coverage in younger adults with chronic conditions. To assess contemporary patterns of pneumococcal vaccination and revaccination of adults, we conducted a cross-sectional study of adults enrolled in medical care organizations (MCOs participating in the Vaccine Safety Datalink project. Methods The study population included 1.5 million adults 25 years of age and older enrolled in the four participating MCOs on December 1, 2006. PPVs administered to members of the study population prior to that date were identified from computerized immunization registries maintained by the MCOs. Results Among the general population of adults 25 through 64 years of age, vaccine coverage increased from 2% in the 25–29 year old age-group to 26% in the 60–64 year old age-group. In all age-groups, coverage was substantially higher in persons defined as having a chronic high risk condition. This was particularly true for diabetes mellitus, with vaccine coverage of over 50% in the lower age-groups and 75% in those 60–64 years of age. Among adults 65 years of age and older, 82% had received at least one PPV and 18% had received two or more PPVs. Conclusion We found higher levels of PPV coverage among adults 65 years of age and older and among younger adults with diabetes mellitus than reported by national surveys and for those groups PPV coverage approached the Healthy People 2010 national objectives. These results suggest that achieving those objectives for PPV is possible and
Howitz, Michael Frantz; Harboe, Zitta Barrella; Ingels, Helene
Introduction of Pneumococcal Conjugated Vaccines (PCV) in national immunization programs have been successful in reducing the number of invasive and lower respiratory pneumococcal infections. The impact of the vaccines on upper respiratory infections caused by pneumococci is less clear although...... these account for most pneumococcal infections. In this study, we used likely proxies for respiratory infections in children, such as antibiotic use and ventilation tube insertions (VTI), to estimate the impact of the vaccine on a national level. The study was designed as a population-based retrospective...... reversed to near year 2000 levels after the introduction of PCV. This indicates that implementation of pneumococcal vaccines in the Childhood Vaccination Programme has likely reduced the incidence of upper respiratory diseases due to pneumococci in Denmark....
Wen, Yu-Wen; Wu, Hsin; Chang, Chee-Jen
Vaccination can reduce the incidence and mortality of an infectious disease and thus increase the years of life and productivity for the entire society. But when determining the vaccination coverage rate, its economic burden is usually not taken into account. This article aimed to use a dynamic transmission modeling (DTM), which is based on a susceptible-infectious-recovered model and is a system of differential equations, to find the optimal vaccination coverage rate based on the economic burden of an infectious disease. Vaccination for pneumococcal diseases was used as an example to demonstrate the main purpose. 23-Valent pneumococcal polysaccharide vaccines (PPV23) and 13-valent pneumococcal conjugate vaccines (PCV13) have shown their cost-effectiveness in elderly and children, respectively. Scenarios analysis of PPV23 to elderly aged 65+ years and of PCV13 to children aged 0 to 4 years was applied to assess the optimal vaccination coverage rate based on the 5-year economic burden. Model parameters were derived from Taiwan's National Health Insurance Research Database, government data, and published literature. Various vaccination coverage rates, the vaccine efficacy, and all epidemiologic parameters were substituted into DTM, and all differential equations were solved in R Statistical Software. If the coverage rate of PPV23 for the elderly and of PCV13 for the children both reach 50%, the economic burden due to pneumococcal disease will be acceptable. This article provided an alternative perspective from the economic burden of diseases to obtain a vaccination coverage rate using the DTM. This will provide valuable information for vaccination policy decision makers. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Full Text Available Traditional genetic association studies are very difficult in bacteria, as the generally limited recombination leads to large linked haplotype blocks, confounding the identification of causative variants. Beta-lactam antibiotic resistance in Streptococcus pneumoniae arises readily as the bacteria can quickly incorporate DNA fragments encompassing variants that make the transformed strains resistant. However, the causative mutations themselves are embedded within larger recombined blocks, and previous studies have only analysed a limited number of isolates, leading to the description of "mosaic genes" as being responsible for resistance. By comparing a large number of genomes of beta-lactam susceptible and non-susceptible strains, the high frequency of recombination should break up these haplotype blocks and allow the use of genetic association approaches to identify individual causative variants. Here, we performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs and indels that could confer beta-lactam non-susceptibility using 3,085 Thai and 616 USA pneumococcal isolates as independent datasets for the variant discovery. The large sample sizes allowed us to narrow the source of beta-lactam non-susceptibility from long recombinant fragments down to much smaller loci comprised of discrete or linked SNPs. While some loci appear to be universal resistance determinants, contributing equally to non-susceptibility for at least two classes of beta-lactam antibiotics, some play a larger role in resistance to particular antibiotics. All of the identified loci have a highly non-uniform distribution in the populations. They are enriched not only in vaccine-targeted, but also non-vaccine-targeted lineages, which may raise clinical concerns. Identification of single nucleotide polymorphisms underlying resistance will be essential for future use of genome sequencing to predict antibiotic sensitivity in clinical microbiology.
Soneji, Samir; Metlay, Joshua
We determined the effectiveness of a 23-valent-polysaccharide pneumococcal vaccine (PPV-23) and pneumococcal conjugate vaccine (PCV-7) in reducing adult pneumococcal mortality by comparing historically predicted declines in pneumococcal disease mortality with observed patterns since the introduction of PPV-23 and PCV-7, including analyses of age, gender, and racial/ethnic subgroups. We analyzed all deaths registered on U.S. death certificates reporting any site of pneumococcal infection (e.g., meningitis, sepsis, pneumonia, bacteremia, and peritonitis) from 1968 to 2006. We used time-series dynamic linear regression on annual pneumococcal mortality rates to determine the percentage reduction in post-1983 mortality rates for a given increase in PPV-23 vaccination rates and post-2000 mortality rates for a given increase in PCV-7 vaccination rates. Pneumococcal mortality decreased well before the introduction of PPV-23 in 1983 and again before the introduction of PCV-7 in 2000. The level of PPV-23 vaccination was associated with a direct and significant reduction in adult mortality, especially white female adults > or = 65 years of age. In contrast, the level of PCV-7 vaccination in the population was not associated with an indirect and significant reduction in pneumococcal mortality beyond the historical pace of decline. PPV-23 introduction was associated with a reduction in pneumococcal mortality among older adults > or = 65 years of age beyond levels predicted by secular trends, whereas PCV-7 introduction was not. Mortality reduction was not uniformly experienced across the population, revealing the need for additional strategies to reduce pneumococcal mortality in older adults.
Lancelot W H Mui
Full Text Available OBJECTIVE: To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50-64 and elderly population (over 65 in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups. DESIGN: Cross-sectional study of general practitioners in private practice in Hong Kong. PARTICIPANTS: Members of Hong Kong Medical Association delivering general practice services in private sector. MEASURING TOOL: Self-administered questionnaire. MAIN OUTCOME MEASURES: Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination. RESULTS: 53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%. Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (ORm 10.1, and attending 6 pneumonia cases or more per year (ORm 2.28 were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (ORm 0.41, consultation not related to vaccination (ORm 0.45 and limited time (ORm 0.38 were factors that reduced the likelihood. CONCLUSION: Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures.
Postma, M J; Heijnen, M L A; Beutels, Ph; Jager, J C
To assess the cost-effectiveness of vaccination to prevent invasive pneumococcal disease in the elderly. Review of the literature. Articles in Dutch or English reporting studies into the cost-effectiveness of vaccination for the prevention of invasive pneumococcal infection in persons over 65 years of age were retrieved from Medline (1980-2000; search terms: 'pneumococcal' and 'vaccine' in combination with 'costs' or 'economics') and on the basis of the reference lists in the articles found. The following aspects of the selected studies were assessed: the net costs per year of life gained, the incidence of invasive pneumococcal disease in the elderly, the mortality due to invasive pneumococcal infections, the effectiveness of the vaccine in the prevention of invasive pneumococcal infections, and the costs of the vaccine and its administration. Attention was also given to specific age categories and to the effects of varying certain crucial assumptions. We retrieved a total of five studies: one each for the USA, Canada, the Netherlands and Spain and a multinational study for five European countries. The cost-effectiveness of vaccination of the elderly against invasive pneumococcal infections varied from cost savings to [symbol: see text] 33,000,-per life-year gained. The Dutch study estimated the cost-effectiveness at [symbol: see text] 10,100,-per life-year gained (price level 1995). Almost all the studies selected based their estimate of the effectiveness of vaccination on the same case-control study from the USA. The potential effects on cost-effectiveness of more extensive influenza vaccination and of the inclusion of re-vaccination against pneumococci were not included in the analyses. The cost-effectiveness of vaccination against invasive pneumococcal infections in persons over 65 years of age (in the Netherlands as well as in several other countries) was below the previously accepted threshold of [symbol: see text] 20,000,-.
González Martínez, F; Navarro Gómez, M L; Saavedra Lozano, J; Santos Sebastián, M M; Rodríguez Fernández, R; González Sanchéz, M; Cercenado Mansilla, E; Hernández-Sampelayo Matos, T
There has been an increased incidence in invasive pneumococcal disease (IPD) produced by non-vaccine serotype (NVS) of Streptococcus pneumoniae after the introduction of PCV7. Our objective was to describe the epidemiological, clinical and microbiological characteristics of IPD caused by NVS in a tertiary hospital in Madrid. Retrospective (1998-2004) and prospective (2005-2009) study evaluating IPD caused by NVS in children. The study was divided into three periods: P1 (1998-2001) when PCV7 was not commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. We analyzed 155 cases of IPD. One hundred and fifty of these isolates were serotyped (100 were NVS). There was an increase in the prevalence of IPD from P1 (31%) to P2 (54%) and P3 (91%). The most relevant emerging serotypes were 19A, 7F, 1, 5, 3 and 15C. The most significant clinical syndromes produced by some specific serotypes were as follows: lower respiratory tract infection (LRTI) by serotypes 1, 3, 5 and 15C; LRTI, primary bacteremia and meningitis by serotype 19A; and primary bacteremia by serotype 7F (66%). The large majority (83.8%) of NVS were sensitive to penicillin. There has been an increased prevalence of IPD caused by NVS since the introduction of PCV7. These changes should prompt the introduction of new pneumococcal vaccines, which include most of the NVS, in the childhood immunization calendar to prevent IPD in children. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Cho, Ying-Chun; Chiu, Nan-Chang; Lu, Chun-Yi; Huang, Daniel Tsung-Ning; Huang, Fu-Yuan; Chang, Luan-Yin; Huang, Li-Min; Chi, Hsin
After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy. S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities. Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.
Full Text Available Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13 versus the 23-valent polysaccharide vaccine (PPSV23 in HIV-infected adults.We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50 received two doses of PCV13 eight weeks apart, and group 2 (n = 50 received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100 were also enrolled as baseline controls.Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group.In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated.ClinicalTrials.gov NCT02123433.
Wu, David Bin-Chia; Roberts, Craig; Lee, Vivian Wing Yan; Hong, Li-Wen; Tan, Kah Kee; Mak, Vivienne; Lee, Kenneth Kwing Chin
Pneumococcal disease causes large morbidity, mortality and health care utilization and medical and non-medical costs, which can all be reduced by effective infant universal routine immunization programs with pneumococcal conjugate vaccines (PCV). We evaluated the clinical and economic benefits of such programs with either 10- or 13-valent PCVs in Malaysia and Hong Kong by using an age-stratified Markov cohort model with many country-specific inputs. The incremental cost per quality-adjusted life year (QALY) was calculated to compare PCV10 or PCV13 against no vaccination and PCV13 against PCV10 over a 10-year birth cohort's vaccination. Both payer and societal perspectives were used. PCV13 had better public health and economic outcomes than a PCV10 program across all scenarios considered. For example, in the base case scenario in Malaysia, PCV13 would reduce more cases of IPD (+2,296), pneumonia (+705,281), and acute otitis media (+376,967) and save more lives (+6,122) than PCV10. Similarly, in Hong Kong, PCV13 would reduce more cases of IPD cases (+529), pneumonia (+172,185), and acute otitis media (+37,727) and save more lives (+2,688) than PCV10. During the same time horizon, PCV13 would gain over 74,000 and 21,600 additional QALYs than PCV10 in Malaysia and Hong Kong, respectively. PCV13 would be cost saving when compared against similar program with PCV10, under both payer and societal perspective in both countries. PCV13 remained a better choice over PCV10 in multiple sensitivity, scenario, and probabilistic analyses. PCV13s broader serotype coverage in its formulation and herd effect compared against PCV10 were important drivers of differences in outcomes. PMID:26451658
Wu, David Bin-Chia; Roberts, Craig; Lee, Vivian Wing Yan; Hong, Li-Wen; Tan, Kah Kee; Mak, Vivienne; Lee, Kenneth Kwing Chin
Pneumococcal disease causes large morbidity, mortality and health care utilization and medical and non-medical costs, which can all be reduced by effective infant universal routine immunization programs with pneumococcal conjugate vaccines (PCV). We evaluated the clinical and economic benefits of such programs with either 10- or 13-valent PCVs in Malaysia and Hong Kong by using an age-stratified Markov cohort model with many country-specific inputs. The incremental cost per quality-adjusted life year (QALY) was calculated to compare PCV10 or PCV13 against no vaccination and PCV13 against PCV10 over a 10-year birth cohort's vaccination. Both payer and societal perspectives were used. PCV13 had better public health and economic outcomes than a PCV10 program across all scenarios considered. For example, in the base case scenario in Malaysia, PCV13 would reduce more cases of IPD (+2,296), pneumonia (+705,281), and acute otitis media (+376,967) and save more lives (+6,122) than PCV10. Similarly, in Hong Kong, PCV13 would reduce more cases of IPD cases (+529), pneumonia (+172,185), and acute otitis media (+37,727) and save more lives (+2,688) than PCV10. During the same time horizon, PCV13 would gain over 74,000 and 21,600 additional QALYs than PCV10 in Malaysia and Hong Kong, respectively. PCV13 would be cost saving when compared against similar program with PCV10, under both payer and societal perspective in both countries. PCV13 remained a better choice over PCV10 in multiple sensitivity, scenario, and probabilistic analyses. PCV13s broader serotype coverage in its formulation and herd effect compared against PCV10 were important drivers of differences in outcomes.
Yang, Tae Un; Kim, Eunsung; Park, Young-Joon; Kim, Dongwook; Kwon, Yoon Hyung; Shin, Jae Kyong; Park, Ok
Although pneumococcal vaccines had been recommended for the elderly population in South Korea for a considerable period of time, the coverage has been well below the optimal level. To increase the vaccination rate with integrating the pre-existing public health infrastructure and governmental funding, the Korean government introduced an elderly pneumococcal vaccination into the national immunization program with a 23-valent pneumococcal polysaccharide vaccine in May 2013. The aim of this study was to assess the performance of the program in increasing the vaccine coverage rate and maintaining stable vaccine supply and safe vaccination during the 20 months of the program. We qualitatively and quantitatively analyzed the process of introducing and the outcomes of the program in terms of the systematic organization, efficiency, and stability at the national level. A staggered introduction during the first year utilizing the public sector, with a target coverage of 60%, was implemented based on the public demand for an elderly pneumococcal vaccination, vaccine supply capacity, vaccine delivery capacity, safety, and sustainability. During the 20-month program period, the pneumococcal vaccine coverage rate among the population aged ≥65 years increased from 5.0% to 57.3% without a noticeable vaccine shortage or safety issues. A web-based integrated immunization information system, which includes the immunization registry, vaccine supply chain management, and surveillance of adverse events following immunization, reduced programmatic errors and harmonized the overall performance of the program. Introduction of an elderly pneumococcal vaccination in the national immunization program based on strong government commitment, meticulous preparation, financial support, and the pre-existing public health infrastructure resulted in an efficient, stable, and sustainable increase in vaccination coverage. Copyright © 2016. Published by Elsevier Ltd.
Effect of Tdap when administered before, with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial.
Tashani, M; Alfelali, M; Barasheed, O; Alqahtani, A S; Heron, L; Wong, M; Rashid, H; Booy, R
Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3-4weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3-4weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18-64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse
Chaiyakunapruk, Nathorn; Somkrua, Ratchadaporn; Hutubessy, Raymond; Henao, Ana Maria; Hombach, Joachim; Melegaro, Alessia; Edmunds, John W; Beutels, Philippe
Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example
van den Biggelaar, Anita H J; Pomat, William; Bosco, Anthony; Phuanukoonnon, Suparat; Devitt, Catherine J; Nadal-Sims, Marie A; Siba, Peter M; Richmond, Peter C; Lehmann, Deborah; Holt, Patrick G
Concerns about the risk of inducing immune deviation-associated "neonatal tolerance" as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death. Copyright © 2011 Elsevier Ltd. All rights reserved.
Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.
Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167
Grant A Mackenzie
Full Text Available Routine use of pneumococcal conjugate vaccines (PCVs in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.
Full Text Available In 2010, 13-valent pneumococcal conjugate vaccine (PCV13 was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100. We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geocoding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls, but less affluent than enrolled controls (52.9% of whom had private insurance. Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8–91.9%; adjusted estimate: 82.5%, 95% CI 65.6–91.1%. In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES. Keywords: Socioeconomic status, PCV13, Pneumococcus, Pneumococcal vaccine, Vaccine effectiveness, Matched case-control
Full Text Available Abstract Background Aboriginal children in remote Australia have high rates of complicated middle ear disease associated with Streptococcus pneumoniae and other pathogens. We assessed the effectiveness of pneumococcal vaccination for prevention of otitis media in this setting. Methods We compared two birth cohorts, one enrolled before (1996–2001, and the second enrolled after introduction of 7-valent pneumococcal conjugate and booster 23-valent polysaccharide vaccine (2001–2004. Source populations were the same for both cohorts. Detailed examinations including tympanometry, video-recorded pneumatic otoscopy and collection of discharge from tympanic membrane perforations, were performed as soon as possible after birth and then at regular intervals until 24 months of life. Analyses (survival, point prevalence and incidence were adjusted for confounding factors and repeated measures with sensitivity analyses of differential follow-up. Results Ninety-seven vaccinees and 51 comparison participants were enrolled. By age 6 months, 96% (81/84 of vaccinees and 100% (41/41 of comparison subjects experienced otitis media with effusion (OME, and by 12 months 89% and 88% experienced acute otitis media (AOM, 34% and 35% experienced tympanic membrane perforation (TMP and 14% and 23% experienced chronic suppurative otitis media (CSOM. Age at the first episode of OME, AOM, TMP and CSOM was not significantly different between the two groups. Adjusted incidence of AOM (incidence rate ratio: 0.88 [95% confidence interval (CI: 0.69–1.13] and TMP (incidence rate ratio: 0.63 [0.36–1.11] was not significantly reduced in vaccinees. Vaccinees experienced less recurrent TMP, 9% (8/95 versus 22% (11/51, (odds ratio: 0.33 [0.11–1.00]. Conclusion Results of this study should be interpreted with caution due to potential bias and confounding. It appears that introduction of pneumococcal vaccination among Aboriginal infants was not associated with significant changes
Durando, Paolo; Rosselli, Roberto; Cremonesi, Ilaria; Orsi, Andrea; Albanese, Erika; Barberis, Ilaria; Paganino, Chiara; Trucchi, Cecilia; Martini, Mariano; Marensi, Lorenzo; Turello, Valter; Study Group, the Ligurian Pneumococcal; Bregante, Alessandro; Cacciani, Roberto; Iudici, Rocco; La Marca, Diego; Pedano, Leonardo; Petrucci, Amadio Franco; Santolini, Maria; Sbisà, Valentina; Zacconi, Monica
Background In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged ≥70 years. Methods An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted
Straetemans, M.; Palmu, A.; Auranen, K.; Zielhuis, G.A.; Kilpi, T.
OBJECTIVE: To explore the effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion and to search for subgroups in which the vaccine had a higher or lower effect. METHODS: Analyses were performed on data from the Finnish Otitis Media Vaccine Trial, a randomised controlled
Full Text Available Introduction of pneumococcal conjugate vaccines (PCVs of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia.A cluster-randomized (by village trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006. Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults to receive one dose of PCV-7 (11 vaccinated villages or meningococcal serogroup C conjugate vaccine (10 control villages. Cross-sectional surveys (CSSs to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS, and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively. A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively. The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age and adults (≥15 y of age at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04-0.57] and OR = 0.32 [95% CI 0.10-0.98], respectively and at CSS-3 (OR = 0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively. Differences in the prevalence of
Xu, Qingfu; Surendran, Naveen; Verhoeven, David; Klapa, Jessica; Ochs, Martina; Pichichero, Michael E
Due to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model. C57BL/6J infant mice were intramuscularly vaccinated at age 1-3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3-4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48h after challenge. PPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6-24h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden. Trivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation
Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.
Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia
The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Kristin L Moffitt
Full Text Available Mucosal or parenteral immunization with a killed unencapsulated pneumococcal whole cell antigen (WCA with an adjuvant protects mice from colonization by a T(H17 CD4+ cell-mediated mechanism. Using preparative SDS gels, we separated the soluble proteins that compose the WCA in order to identify fractions that were immunogenic and protective. We screened these fractions for their ability to stimulate IL-17A secretion from splenocytes obtained from mice immunized with WCA and adjuvant. We identified 12 proteins within the stimulatory fractions by mass spectrometry; these proteins were then cloned, recombinantly expressed and purified using an Escherichia coli expression system. The ability of these proteins to induce IL-17A secretion was then evaluated by stimulation of mouse splenocytes. Of the four most stimulatory proteins, three were protective in a mouse pneumococcal serotype 6B colonization model. This work thus describes a method for identifying immunogenic proteins from the soluble fraction of pneumococcus and shows that several of the proteins identified protect mice from colonization when used as mucosal vaccines. We propose that, by providing protection against pneumococcal colonization, one or more of these proteins may serve as components of a multivalent pneumococcal vaccine.
Williams, B Adam; Kidane, Teklay; Chirwa, Geoffrey; Tesfaye, Neghist; Prescott, Marta R; Scotney, Soleine T; Valle, Moussa; Abebe, Sintayehu; Tambuli, Adija; Malewezi, Bridget; Mohammed, Tahir; Kobayashi, Emily; Wootton, Emily; Wong, Renee; Dosani, Rahima; Subramaniam, Hamsa; Joseph, Jessica; Yavuz, Elif; Apple, Aliza; Le Tallec, Yann; Kang'ethe, Alice
Understanding post-launch demand for new vaccines can help countries maximize the benefits of immunization programmes. In particular, low- and middle-income countries (LMICs) should ensure adequate resource planning with regards to stock consumption and service delivery for new vaccines, whereas global suppliers must produce enough vaccines to meet demand. If a country underestimates the number of children seeking vaccination, a stock-out of commodities will create missed opportunities for saving lives. We describe the post-launch demand for the first dose of pneumococcal conjugate vaccine (PCV1) in Ethiopia and Malawi and the first dose of rotavirus vaccine (Rota1) in Malawi, with focus on the new birth cohort and the 'backlog cohort', comprised of older children who are still eligible for vaccination at the time of launch. PCV1 and Rota1 uptake were compared with the demand for the first dose of pentavalent vaccine (Penta1), a routine immunization that targets the same age group and immunization schedule. In the first year, the total demand for PCV1 was 37% greater than that of Penta1 in Ethiopia and 59% greater in Malawi. In the first 6 months, the demand of Rota1 was only 5.9% greater than Penta1 demand in Malawi. Over the first three post-introduction months, 70.7% of PCV1 demand in Ethiopia and 71.5% of demand in Malawi came from children in the backlog cohort, whereas only 28.0% of Rota1 demand in Malawi was from the backlog cohort. The composition of demand was impacted by time elapsed since vaccine introduction and age restrictions. Evidence suggests that countries' plans should account for the impact of backlog demand, especially in the first 3 months post-introduction. LMICs should request for higher stock volumes when compared with routine needs, plan social mobilization activities to reach the backlog cohort and allocate human resources and cold chain capacity to accommodate high demand following vaccine introduction. © The Author 2016. Published by
M. S. Naumtseva
Full Text Available Objective: to investigate the immunogenicity, safety, and clinical efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA during a two-year follow-up study.Subjects and methods. The prospective open-label comparative study enrolled 110 people, of them there were 81 (73.6% women and 29 (26.4% men at the age of 23 to 76 years, including 79 patients with RA, as well as 31 subjects without systemic inflammatory rheumatic diseases (RD (a control group. The group of RA patients exhibited a predominance of middle-aged women who had > 3 years’ disease duration and a moderate inflammatory activity (the mean value of DAS28, 4.32. 52 patients received methotrexate (MTX, 14 had Leflunomide (LEF, and 13 were treated with tumor necrosis factor-α (TNF-α inhibitors + MTX.The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France was administered in a single dose of 0.5 ml subcutaneously during continuous MTX or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patient and conventional clinical and laboratory studies were performed during control visits (1, 3, 12, and 24 months after vaccination. Clinical effectiveness and safety were evaluated in all the patients included in the study. The serum levels of anti-pneumococcal capsular polysaccharide antibodies (Ab were measured in 72 patients with RA and in 30 individuals in the control group during a 12-month follow-up study, including in 25 patients with RA for a 24-month follow-up study by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, Birmingham, United Kingdom. Along with this, the post-immunization response coefficient was calculated for each patient as the ratio of postvaccination Ab levels during Visits 2, 3, 4, and 5 to the baseline Ab level. Results and discussion. No clinical and
Silvio D Brugger
Full Text Available Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7.Nasopharyngeal swabs (n 1120 were collected from outpatients between 2004 and 2009 within an ongoing nationwide surveillance program. Cocolonization was detected directly from swabs by restriction fragment length polymorphism (RFLP analysis. Serotypes were identified by agglutination, multiplex PCR and microarray.Rate of multiple colonization remained stable up to three years after PCV7 introduction. Cocolonization was associated with serotypes of low carriage prevalence in the prevaccine era. Pneumococcal colonization density was higher in cocolonized samples and cocolonizing strains were present in a balanced ratio (median 1.38. Other characteristics of cocolonization were a higher frequency at young age, but no association with recurrent acute otitis media, recent antibiotic exposure, day care usage and PCV7 vaccination status.Pneumococcal cocolonization is dominated by serotypes of low carriage prevalence in the prevaccine era, which coexist in the nasopharynx. Emergence of such previously rare serotypes under vaccine selection pressure may promote cocolonization in the future.
Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H
Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged Peru. Copyright © 2016. Published by Elsevier Ltd.
Opstelten, W; Hak, E; Verheij, T J; van Essen, G A
PURPOSE: Influenza vaccination has been recommended for all elderly people in The Netherlands since 1996, with greater than 80% compliance. It is unknown, however, if the addition of another vaccine to this immunization program will affect compliance. SUBJECTS AND METHODS: General practitioners
Immunogenicity and Safety of 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Administered to Children With Sickle Cell Disease Between 8 Weeks and 2 Years of Age: A Phase III, Open, Controlled Study.
Sirima, Sodiomon B; Tiono, Alfred; Gansané, Zakaria; Siribié, Mohamadou; Zongo, Angèle; Ouédraogo, Alphonse; François, Nancy; Strezova, Ana; Dobbelaere, Kurt; Borys, Dorota
Immunogenicity, safety and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in children with sickle cell disease (SCD), who are at increased risk for infections. In this phase III, open-label, single-center, controlled study in Burkina Faso (NCT01175083), children with SCD (S) or without SCD (NS) were assigned to 6 groups (N = 300): children 8-11 weeks of age (vaccines; children 7-11 months of age (7-11S and 7-11NS groups) received 2 primary doses and a booster dose of PHiD-CV; children 12-23 months of age (12-23S and 12-23NS groups) received 2 catch-up doses of PHiD-CV. Pneumococcal antibody responses were measured using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity. Responses to other antigens were measured by enzyme-linked immunosorbent assay. Adverse events were recorded. One month postprimary vaccination, for each vaccine serotype ≥98% of infants in the vaccination in children vaccination. Safety and reactogenicity profiles were similar in children with or without SCD. PHiD-CV was immunogenic with an acceptable safety profile in children with and without SCD starting vaccination at 8 weeks to 23 months of age.
Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro
The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (potitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.
Clarke, Christopher; Bakaletz, Lauren O; Ruiz-Guiñazú, Javier; Borys, Dorota; Mrkvan, Tomas
Protein D-containing vaccines may decrease acute otitis media (AOM) burden and nasopharyngeal carriage of non-typeable Haemophilus influenzae (NTHi). Protein D-containing pneumococcal conjugate vaccine PHiD-CV (Synflorix, GSK Vaccines) elicits robust immune responses against protein D. However, the phase III Clinical Otitis Media and PneumoniA Study (COMPAS), assessing PHiD-CV efficacy against various pneumococcal diseases, was not powered to demonstrate efficacy against NTHi; only trends of protective efficacy against NTHi AOM in children were shown. Areas covered: This review aims to consider all evidence available to date from pre-clinical and clinical phase III studies together with further evidence emerging from post-marketing studies since PHiD-CV has been introduced into routine clinical practice worldwide, to better describe the clinical utility of protein D in preventing AOM due to NTHi and its impact on NTHi nasopharyngeal carriage. Expert commentary: Protein D is an effective carrier protein in conjugate vaccines and evidence gathered from pre-clinical, clinical and observational studies suggest that it also elicits immune response that can help to reduce the burden of AOM due to NTHi. There remains a need to develop improved vaccines for prevention of NTHi disease, which could be achieved by combining protein D with other antigens.
Becker-Dreps, Sylvia; Blette, Bryan; Briceño, Rafaela; Alemán, Jorge; Hudgens, Michael G; Moreno, Gilberto; Ordoñez, Ana; Rocha, Julio; Weber, David J; Amaya, Erick
Streptococcus pneumoniae causes about 826,000 deaths of children in the world each year and many health facility visits. To reduce the burden of pneumococcal disease, many nations have added pneumococcal conjugate vaccines to their national immunization schedules. Nicaragua was the first country eligible for GAVI Alliance funding to introduce the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010, provided to infants at 2, 4, and 6 months of age. The goal of this study was to evaluate the population impact of the first five years of the program. Numbers of visits for pneumonia, pneumonia-related deaths, and bacterial meningitis in both children and adults, and infant deaths between 2008 and 2015 were collected from all 107 public health facilities in León Department. Vital statistics data provided additional counts of pneumonia-related deaths that occurred outside health facilities. Adjusted incidence rates and incidence rate ratios (IRRa) in the vaccine (2011-2015) and pre-vaccine periods (2008-2010) were estimated retrospectively using official population estimates as exposure time. The IRRa for pneumonia hospitalizations was 0.70 (95% confidence interval [CI]: 0.66, 0.75) for infants, and 0.92 (95% CI: 0.85, 0.99) for one year-olds. The IRRa for post-neonatal infant mortality was 0.56 (95% CI: 0.41, 0.77). In the population as a whole, ambulatory visits and hospitalizations for pneumonia, as well as pneumonia-related mortality and rates of bacterial meningitis were lower in the vaccine period. During the first five years of program implementation, reductions were observed in health facility visits for pneumonia in immunized age groups and infant mortality, which would be hard to achieve with any other single public health intervention. Future study is warranted to understand whether the lack of a booster dose (e.g., at 12 months) may be responsible for the small reductions in pneumonia hospitalizations observed in one year-olds as compared to infants.
Bosch, Astrid A T M; van Houten, Marlies A.; Bruin, Jacob P.; Wijmenga-Monsuur, Alienke J.; Trzciński, Krzysztof; Bogaert, Debby; Rots, Nynke Y.; Sanders, Elisabeth A M
After introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A emerged and became the dominant serotype in carriage in children and their parents.
Laursen, B B; Danstrup, C S; Hoffmann, S; Nørskov-Lauritsen, N; Christensen, A L B; Ovesen, T
The objectives of this study were to investigate the incidence of complicated acute otitis media (cAOM) as well as the associated microbiology before and after introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV-7 and -13), respectively. CAOM comprises "heavy" AOM (AOM demanding hospitalization), mastodismus (M) and acute mastoiditis (AM). A retrospective cohort study of the incidence and microbiology associated with cAOM during the non-PCV era, the PCV-7 and 13 eras, respectively. Clinical and microbiological data were prospectively registered in a local database. The incidences of cAOM as well as the distribution of various bacterial strains in the three eras were compared. A total of 246 cases of cAOM (125 in the pre-vaccine period (2001-2006), 50 in the PCV-7 period (2007-2010) and 71 in the PCV-13 period (2011-2015)) were identified. The incidence of hAOM decreased by 62% in the PCV7-era but increased to almost pre-vaccine levels in the PCV-13 era. In the M + AM group, a decrease by almost 21% in the PCV7-era was found compared to the pre vaccine era, whereas the decrease was only 12% in the PCV13-era. The three most common findings in both hAOM and M + AM were Streptococcus pneumonia (SP), group A streptococcus (GAS) and "no growth". In the hAOM group, SP decreased from 38% in the pre-vaccine era to 31% in the PCV7-era and further to 16% in the PCV13-era. GAS decreased from 17% in the pre-vaccine era to 0% in the PCV7-era and 16% in the PCV13-era. The percentage of "no growth" increased from 12% to 38% and 44%, respectively. In the M + AM group, SP decreased to 10% in the PCV13-era compared with 44% in the pre-vaccine era and 41% in the PCV7-era. An increase in GAS from 15% in the pre-vaccine era and PCV7-era to 30% in the PCV13-era was observed. The "no growth" percentage increased from 13% in the pre-vaccine era to 26% in the PCV7-era and 33% in the PCV13-era. Introduction of PCV7 and PCV13 has been associated with an overall
Jolin, Jonathan; van Aalst, Robertus; Volpp, Bryan; Taylor, Thomas; Cohen, Emily
Pneumococcal infections are an important source of morbidity and mortality in older adults and persons with compromised immune systems. New recommendations from the Advisory Committee on Immunization Practices (ACIP) became available September 2014, which included recommendations for the use of the 13-valent pneumococcal conjugate vaccine (PCV13). A study was conducted to increase the PCV13 vaccination rates of hospitalized patients at the White River Junction Veterans Affairs Medical Center (White River Junction, Vermont) through the use of a resident-driven quality improvement (QI) project. From December 2014 through April 2016, 16 internal medicine inpatient residents addressed inpatient PCV13 vaccination rates by participating in the facility's QI curriculum. Eight Plan-Do-Study-Act cycles were used, including discharge template editing, electronic reminders, and the discovery of a vaccination administration documentation error in the record through data validation. The measure was the monthly percentage of patients who received PCV13 vaccination (vaccination completion rate) of those discharged from the hospital medicine service who were due for PCV13 vaccination. The percentage of veterans discharged with an up-to-date PCV13 vaccination on discharge increased from approximately 30% to 87% and was sustained. Despite being driven by many different residents, this project demonstrates that continuous improvement can be achieved through a structured and iterative process while providing active learning of core QI concepts to residents. It also displays a method in which new guidelines can be incorporated into practice in an effective manner. Finally, this project is an example of how resident-driven data validation can lead to further improvement. Published by Elsevier Inc.
Spencer, Brady L.; Shenoy, Anukul T.; Orihuela, Carlos J.; Nahm, Moon H.
As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), carries the putative O-acety...
Ho, Hanley J; Chan, Yin Ying; Ibrahim, Muhamad Alif Bin; Wagle, Anurupa A; Wong, Christina M; Chow, Angela
Adult influenza and pneumococcal vaccination rates in Singapore are low, and factors influencing knowledge and attitudes of seniors towards influenza, pneumonia and their respective vaccines are not well-known. Our study aims to understand the barriers and facilitators towards getting influenza and pneumococcal vaccinations among seniors in Singapore, and subsequently inform the conduct of a relevant community-based educational intervention, as well as evaluate the intervention outcomes. We performed a mixed methods study with two components: Firstly, formative research was conducted among community-dwelling seniors, using focus group discussions (FGDs), to understand their knowledge and attitudes towards influenza, pneumonia and their respective vaccines. Next, a quantitative study was conducted to evaluate knowledge of seniors and the effectiveness of an educational intervention. Four FGDs were organised with 32 participants, who were predominantly female, of lower educational background, and residing in government rental flats. Participants had varying levels of knowledge and many misconceptions about influenza, pneumonia and their respective vaccinations, with concerns about side effects and vaccine effectiveness. The formative research results were used to inform a community-based educational intervention for seniors. Our subsequent evaluation included 604 elderly participants, mainly from lower educational and socio-economic strata, who initially demonstrated poor knowledge scores (median score 5 out of 9, IQR 4-5). Following our intervention, median knowledge score improved to 7 (IQR 6-8) (p seniors which affected their attitudes towards vaccination uptake. Key findings were taken into consideration when implementing the educational intervention. Our community-based intervention was effective in improving knowledge and attitudes, and could be used as a cue to action for short-term behaviour changes. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available Malawi introduced pneumococcal conjugate vaccine (PCV13 and monovalent rotavirus vaccine (RV1 in 2011 and 2012 respectively, and is planning the introduction of a second-dose measles vaccine (MV. We assessed predictors of availability, uptake and timeliness of these vaccines in a rural Malawian setting.Commencing on the first date of PCV13 eligibility we conducted a prospective population-based birth cohort study of 2,616 children under demographic surveillance in Karonga District, northern Malawi who were eligible for PCV13, or from the date of RV1 introduction both PCV13 and RV1. Potential predictors of vaccine uptake and timeliness for PCV13, RV1 and MV were analysed respectively using robust Poisson and Cox regression.Vaccine coverage was high for all vaccines, ranging from 86.9% for RV1 dose 2 to 95.4% for PCV13 dose 1. Median time delay for PCV13 dose 1 was 17 days (IQR 7-36, 19 days (IQR 8-36 for RV1 dose 1 and 20 days (IQR 3-46 for MV. Infants born to lower educated or farming mothers and those living further away from the road or clinic were at greater risk of being not fully vaccinated and being vaccinated late. Delays in vaccination were also associated with non-facility birth. Vaccine stock-outs resulted in both a delay in vaccine timeliness and in a decrease in completion of schedule.Despite high vaccination coverage in this setting, delays in vaccination were common. We identified programmatic and socio-demographic risk factors for uptake and timeliness of vaccination. Understanding who remains most vulnerable to be unvaccinated allows for focussed delivery thereby increasing population coverage and maximising the equitable benefits of universal vaccination programmes.
ASSESSMENT OF TOLERABILITY OF PNEUMOCOCCAL CONJUGATE VACCINE AND THE INFLUENCE OF THE VACCINATION ON THE INCIDENCE OF RESPIRATORY INFECTIONS IN CHILDREN DURING THE FIRST FIVE YEARS OF LIFE IN THE SAKHA REPUBLIC (YAKUTIA
Full Text Available One of the most frequent etiology agent of upper respiratory tract infection is pneumococcus. Most susceptible to this infection are children under 5 years old. It is known that the only effective prevention of pneumococcal infections is a specific immunoprophylaxis. Authors represent their own experience of vaccination for the child population at risk. The analysis of the effectiveness of 7-valent conjugate pneumococcal vaccine in 596 children under 5 years old is demonstrated. The immunization is revealed low reactogeni city of vaccine and evident clinical effect. Thus, this vaccine may be recommended for inclusion in a regional immunization schedule in Republic of Sakha (Yakutia.Key words: children, pneumococcal infection, vaccine prophylaxis.
Warren, Joshua L.; Shioda, Kayoko; Kürüm, Esra
Background Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used...... to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries. Methods We evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle......-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine...
Newall, A T; Reyes, J F; McIntyre, P; Menzies, R; Beutels, P; Wood, J G
Retrospective cost-effectiveness analyses of vaccination programs using routinely collected post-implementation data are sparse by comparison with pre-program analyses. We performed a retrospective economic evaluation of the childhood 7-valent pneumococcal conjugate vaccine (PCV7) program in Australia. We developed a deterministic multi-compartment model that describes health states related to invasive and non-invasive pneumococcal disease. Costs (Australian dollars, A$) and health effects (quality-adjusted life years, QALYs) were attached to model states. The perspective for costs was that of the healthcare system and government. Where possible, we used observed changes in the disease rates from national surveillance and healthcare databases to estimate the impact of the PCV7 program (2005-2010). We stratified our cost-effectiveness results into alternative scenarios which differed by the outcome states included. Parameter uncertainty was explored using probabilistic sensitivity analysis. The PCV7 program was estimated to have prevented ∼5900 hospitalisations and ∼160 deaths from invasive pneumococcal disease (IPD). Approximately half of these were prevented in adults via herd protection. The incremental cost-effectiveness ratio was ∼A$161,000 per QALY gained when including only IPD-related outcomes. The cost-effectiveness of PCV7 remained in the range A$88,000-$122,000 when changes in various non-invasive disease states were included. The inclusion of observed changes in adult non-invasive pneumonia deaths substantially improved cost-effectiveness (∼A$9000 per QALY gained). Using the initial vaccine price negotiated for Australia, the PCV7 program was unlikely to have been cost-effective (at conventional thresholds) unless observed reductions in non-invasive pneumonia deaths in the elderly are attributed to it. Further analyses are required to explore this finding, which has significant implications for the incremental benefit achievable by adult PCV
Full Text Available Abstract Background Conflicting results have been recently reported evaluating the relationship between pneumococcal vaccination and the risk of thrombotic vascular events. This study assessed the clinical effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23 against acute myocardial infarction and ischaemic stroke in older adults. Methods Population-based prospective cohort study conducted from December 1, 2008 until November 30, 2009, including all individuals ≥ 60 years-old assigned to nine Primary Care Centres in Tarragona, Spain (N = 27,204 individuals. Primary outcomes were hospitalisation for acute myocardial infarction and/or ischaemic stroke. All cases were validated by checking clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by Multivariable Cox proportional-hazard models (adjusted by age, sex, influenza vaccine status, presence of comorbidities and cardiovascular risk factors. Results Cohort members were followed for a total of 26,444 person-years, of which 34% were for vaccinated subjects. Overall incidence rates (per 1000 person-years were 4.9 for myocardial infarction and 4.6 for ischaemic stroke. In the multivariable analysis, vaccination was associated with a marginally significant 35% lower risk of stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.42-0.99; p = 0.046. We found no evidence for an association between pneumococcal vaccination and reduced risk of myocardial infarction (HR: 0.83; 95% CI: 0.56-1.22; p = 0.347. Conclusions Our data supports a benefit of PPV23 against ischaemic stroke among the general population over 60 years, suggesting a possible protective role of pneumococcal vaccination against some acute thrombotic events.
Leemans, R; Manson, W; Snijder, JAM; Smit, JW; Klasen, HJ; The, TH; Timens, W
Objective To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. Summary Background Data After splenectomy, patients
Full Text Available INTRODUCTION In Serbia, there is a significant number of persons suffering of pneumococcal pneumonia. Persons aged 65 years or older, immunocompromised patients, patients with co-morbidities, such as chronic obstructive lung disease and congestive heart failure, are at the highest risk for developing pneumococcal pneumonia. Most of the patients are treated empirically, although it is often overlooked that Streptococcus pneumoniae can be resistant to the used antibiotics. The treatment costs of such inpatients and outpatients are very high. In Serbia, immunization of persons at risk to develop the diseases caused by Streptococcus pneumoniae is carried out using pneumococcus polysaccharide vaccine according to clinical indications. The exact number of immunized persons and the total number of registered patients are still unknown, but it is certain of being unjustifiably low. OBJECTIVE The goal of the study was to investigate, during a one-year period, the number and basic characteristics of persons hospitably treated for pneumonia, the type of cause of the infection, applied antibiotic medications, duration and costs of hospital treatment at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade. METHOD We retrospectively analyzed the medical records of patients with pneumonia treated at the Institute for Lung Diseases and Tuberculosis of the Clinical Centre of Serbia in Belgrade during 2006. RESULTS During the observed one-year period, 290 patients underwent hospital treatment, of whom the cause of the infection was confirmed in 116 (40%. The average duration of hospitalization was 12 days, with treatment cost of 32,031.74 RSD (402.42 EUR per patient. The treatment cost per patient including general and intensive care was 18,290.01 RSD (229.78 EUR. The distribution cost of Pneumo 23 vaccine in Serbia, without purchase tax, was 746.90 RSD (9.38 EUR. CONCLUSION Pneumococcal pneumonia is a significant medical
General health, otitis media, nasopharyngeal carriage and middle ear microbiology in Northern Territory Aboriginal children vaccinated during consecutive periods of 10-valent or 13-valent pneumococcal conjugate vaccines.
Leach, Amanda J; Wigger, Christine; Beissbarth, Jemima; Woltring, Donna; Andrews, Ross; Chatfield, Mark D; Smith-Vaughan, Heidi; Morris, Peter S
This study aims to monitor the prevalence of suppurative otitis media in remote Indigenous communities after introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2011. We previously reported a decline in suppurative OM following replacement of PCV7 by 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) in October 2009. We continued regular surveillance in remote Indigenous communities between February 2010 and August 2013. This analysis reports the general health, otitis media (OM), nasopharyngeal (NP) carriage and middle ear microbiology in children less than 36 months of age who received a primary course of at least two doses of PHiD-CV10 or PCV13, and not more than one dose of another pneumococcal vaccine. Mean ages of 511 PHiD-CV10- and 140 PCV13-vaccinated children were 19 and 13 months, respectively. Most children received 3-dose non-mixed PCV schedules. At the time of assessment, general health was poor and prevalence of risk factors was high in both groups: overall, around 14% of children had scabies, 20% had impetigo, 59% had runny nose and 39% had cough. Average household size was 8 persons, and 60% of the mothers smoked. Bilaterally normal middle ears were detected in 10% and 7%, respectively. OM with effusion (OME), almost all bilateral, was diagnosed in 52% and 50%, any suppurative OM (acute OM or any tympanic membrane perforation [TMP]) in 37% and 41%, and TMP in 14% and 12%, respectively. Children in the PCV13 group had significantly less NP carriage of combined Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) (62% versus 51%) but significantly more polymicrobial (Spn and NTHi) middle ear cultures (12% versus 43%), and significantly less Staphylococcus aureus-positive middle ears (40% versus 7%). Although NP carriage of pneumococcal serotype 19A was low in the PCV13 group, serotypes 19F and 23F persist. The general health, particularly ear health, of little children
González Martínez, F; Saavedra Lozano, J; Navarro Gómez, M L; Santos Sebastián, M M; Rodríguez Fernández, R; González Sánchez, M; Hernández-Sampelayo Matos, T
To describe the epidemiology, clinical syndromes and microbiological characteristics of serotype 19A as the main cause of invasive pneumococcal disease (IPD) in children admitted to a tertiary hospital in Spain. A retrospective (1998-2004) and prospective (2005-2009) study was conducted on children with IPD produced by serotype 19A. The study was divided into three periods (P): P1 (1998-2001) when PCV7 had not been commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. A total of 155 isolates of Streptococcus pneumoniae (SP) producing IPD were analysed, with 21 of them being serotype 19A (14%). An increased prevalence of serotype 19A was found: 2/45 cases (4.4%) in P1, 3/41 cases (7.3%) in P2 and 16/69 cases (23.2%) in P3. It occurred mostly in children younger than 2 years (16/21; 76%). This serotype was the main cause of meningitis (5/20; 25%), pleural empyema (3/22; 14%) and bacteraemic mastoiditis (2/4; 50%). Thirteen isolates (61.5%) had an MIC ≥ 0.12μ/ml for penicillin in extra-meningeal infections, and 3 of the 5 isolates causing meningitis (60%) had an MIC ≥ 1μ/ml for cefotaxime. Serotype 19A was the main causal agent of IPD in the PCV7 era (P3), with high antibiotic resistance rates. This serotype was responsible for all types of IPD, being the main cause of meningitis. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Bjornson, AB; Falletta, JM; Verter, JI; Buchanan, GR; Miller, ST; Pegelow, CH; Iyer, RV; Johnstone, HS; DeBaun, MR; Wethers, DL; Woods, GM; Holbrook, CT; Becton, DL; Kinney, TR; Reaman, GH; Kalinyak, K; Grossman, NJ; Vichinsky, E; Reid, CD
Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years ski children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. Study design:
Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping
To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.
Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond
Abstract Background PCV13 replaced 7-valent pneumococcal conjugate vaccine in the routine infant immunization schedule in Mexico since 2011. The use of PCV13 has reduced pneumococcal disease incidence for vaccine serotypes, particularly 19A, which emerged following PCV7 use. The 10-valent vaccine (PCV10) contains the same serotypes as PCV13 with the exception of serotypes 3, 19A and 6A but also has different conjugated proteins for the common serotypes. This study evaluated the potential health and economic implications of switching from PCV13 to PCV10 in Mexico. Methods A decision-analytic model was developed to estimate public health and economic impact of maintaining PCV13 compared with switching to PCV10 in Mexico. Disease incidence at time of potential switch for invasive pneumococcal disease (IPD), pneumonia (PNE) and acute otitis media (AOM) was obtained from Dirección General de Epidemiología and the published literature. Historical data was used to estimate IPD trends under different infant vaccine pressures and the model forecasted disease across the population. For each vaccination program, health outcomes and associated health-care costs were estimated. Costs, utility weights, and risk of disease-specific complications were derived from published sources. Results In the base case, continued use of PCV13 would result in significantly fewer cases of pneumococcal disease than switching to PCV10 in Mexico (See Table 1). Despite a higher vaccine cost, PCV13 was cost-saving compared with PCV10 in the base case and across a number of scenarios evaluated. Table 1: Total cases and costs associated with maintaining use of PCV13 vs. switching to PCV10 in Mexico over a 10 year period PCV13 PCV10 Difference IPD 16,808 17,248 −440 AOM 7,023,448 7,245,446 −221,998 PNE 1,743,115 1,831,936 −88,821 Deaths 19,457 19,867 −410 Total QALYs 864,069,669 864,068,101 1,568 Total Cost $258,353,508,707 $264,927,566,637 −$6,574,057,930 ICER PCV13 Dominant Costs are
William S Pomat
Full Text Available Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7 given in a 0-1-2-month (neonatal schedule with that of the routine 1-2-3-month (infant schedule.We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV at age 9 months. Serotype-specific serum IgG for PCV7 (VT serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs and proportions with concentration ≥ 0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001 and 9V (p<0.05 and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001 at age 2 months in the neonatal (one month post-dose2 PCV7 than in the infant group (one month post-dose1 PCV7. PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months.PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.ClinicalTrials.gov NCT00219401.
Ekaterina I. Alexeeva
Full Text Available Background. Patients with juvenile idiopathic arthritis (JIA have an increased risk of being infected. Approximately half of all serious infections in children with JIA are associated with airway involvement.Objective. Our aim was to study the efficacy and safety of the pneumococcal 13-valent conjugate vaccine (PCV in children with JIA.Methods. In a prospective cohort study, 5 groups were formed: children with JIA in the remission phase on methotrexate therapy (group 1 or etanercept (group 2, with JIA in the active phase prior to the appointment of methotrexate (group 3 or etanercept (group 4, control group (conditionally healthy children. 0.5 ml of the 13-valent PCV was administered once subcutaneously during therapy in patients in the remission phase or 3 weeks before the appointment of methotrexate or etanercept in patients in the active phase. The main study outcome was the proportion of patients with a protective ( 40 mg/L level of specific anti-pneumococcal antibodies (anti-SPP IgG to Streptococcus pneumoniae 4 weeks after vaccination. In addition, we assessed the incidence of infectious events before and after vaccination as well as changes in the content of a high-sensitivity C-reactive protein, S100 protein, and post-vaccination period.Results. The study included 125 children. Four weeks after vaccination, the protective level of anti-SPP IgG was established in 21 (84% patients in the 1st, 23 (92% in the 2nd, 22 (88% in the 3rd, 24 (96% in the 4th and 5th groups (p =1.0. Increase in the concentration of S100 protein and high-sensitivity C-reactive protein after vaccination was not noted. JIA exacerbation episodes were not recorded in any patient. After immunization, the total number of infectious events decreased in all observed groups (p 0.001. Serious adverse events were not registered during the study.Conclusion. Vaccination with the 13-valent PCV in children with JIA is highly effective
Gyhrs, A; Pedersen, B K; Bygbjerg, I; Henrichsen, J; Heron, I; Petersen, I; Skinhoj, P
In vitro studies have shown that anti-malarial drugs suppress immunity. In this study, the effects of chloroquine and proguanil (Paludrine) on the cellular and humoral immune system were measured by two in vivo methods: 1) cell-mediated immunity (delayed cutaneous hypersensitivity) i.e., skin tests with seven delayed-type common antigens (Multitest) and 2) humoral immunity by measurement of specific antibody response to vaccination. Sixty healthy young individuals were randomized into four groups and given 1) no treatment (controls), 2) chloroquine diphosphate (500 mg/week), 3) chloroquine diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test. The results showed that there were no significant differences among the four groups regarding skin test areas and increases in antibody titers following vaccination. Therefore, it is concluded that in healthy persons, six weeks intake of chloroquine, even in double doses, or proguanil in chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens.
Lehmann, Deborah; Kirarock, Wendy; van den Biggelaar, Anita H J; Passey, Megan; Jacoby, Peter; Saleu, Gerard; Masiria, Geraldine; Nivio, Birunu; Greenhill, Andrew; Orami, Tilda; Francis, Jacinta; Ford, Rebecca; Kirkham, Lea-Ann; Solomon, Vela; Richmond, Peter C; Pomat, William S
Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5 th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal
Pneumococcal meningitis; Pneumococcus - meningitis ... Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type of bacteria is the ...
Full Text Available BACKGROUND: We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7 programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. METHODS AND FINDINGS: Nasopharyngeal swabs were taken from children <5 y old and family members (n=400 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49. The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. CONCLUSION: Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.
Tetanus-diphtheria-pertussis vaccine may suppress the immune response to subsequent immunization with pneumococcal CRM197-conjugate vaccine (coadministered with quadrivalent meningococcal TT-conjugate vaccine): a randomized, controlled trial⋆.
Tashani, Mohamed; Heron, Leon; Wong, Melanie; Rashid, Harunor; Booy, Robert
: Due to their antigenic similarities, there is a potential for immunological interaction between tetanus/diphtheria-containing vaccines and carrier proteins presented on conjugate vaccines. The interaction could, unpredictably, result in either enhancement or suppression of the immune response to conjugate vaccines if they are injected soon after or concurrently with diphtheria or tetanus toxoid. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage of 2015. We randomly assigned each participant to one of three vaccination schedules. Group A received tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) coadministered with TT-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines concurrently. Group C received PCV13 and MCV4 3-4 weeks before Tdap. Blood samples collected at baseline, at each vaccination visit and 3-4 weeks after vaccination were tested for the pneumococcal opsonophagocytic assay (OPA). A total of 166 participants aged 18-64 (median 42) years were recruited, 159 completed the study. Compared with the other groups, Group A had significantly ( P vaccination in seven serotypes of PCV13 (1, 3, 4, 5, 14, 18C and 9V). Additionally, Group A had lower frequency of serorises (≥ 4-fold rise in OPA titres) in serotype5 (79%, p = 0.01) and 18C (73.5%, p = 0.06); whereas Groups B and C had significantly lower frequencies of serorises in Serotype 4 (82%) and 6A (73.5%), respectively. No statistically significant difference was detected across the three groups in frequencies achieving OPA titre ≥ 1:8 post-vaccination. Tdap vaccination 3-4 weeks before administration of PCV13 and MCV4 significantly reduced the GMTs to seven of the 13 pneumococcal serotypes in adults. If multiple vaccination is required before travel, deferring tetanus/diphtheria until after administering the
Frederiksen, B; Specht, L; Henrichsen, J
response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response....
Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia.
Urbancikova, Ingrid; Prymula, Roman; Goldblatt, David; Roalfe, Lucy; Prymulova, Karolina; Kosina, Pavel
Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12-15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11-12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1month post-booster. A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27). Copyright © 2017 Elsevier Ltd
Wallace, Lauren; Kapirir, Lydia
To date, research on priority-setting for new vaccines has not adequately explored the influence of the global, national and sub-national levels of decision-making or contextual issues such as political pressure and stakeholder influence and power. Using Kapiriri and Martin's conceptual framework, this paper evaluates priority setting for new vaccines in Uganda at national and sub-national levels, and considers how global priorities can influence country priorities. This study focuses on 2 specific vaccines, the human papilloma virus (HPV) vaccine and the pneumococcal conjugate vaccine (PCV). This was a qualitative study that involved reviewing relevant Ugandan policy documents and media reports, as well as 54 key informant interviews at the global level and national and sub-national levels in Uganda. Kapiriri and Martin's conceptual framework was used to evaluate the prioritization process. Priority setting for PCV and HPV was conducted by the Ministry of Health (MoH), which is considered to be a legitimate institution. While respondents described the priority setting process for PCV process as transparent, participatory, and guided by explicit relevant criteria and evidence, the prioritization of HPV was thought to have been less transparent and less participatory. Respondents reported that neither process was based on an explicit priority setting framework nor did it involve adequate representation from the districts (program implementers) or publicity. The priority setting process for both PCV and HPV was negatively affected by the larger political and economic context, which contributed to weak institutional capacity as well as power imbalances between development assistance partners and the MoH. Priority setting in Uganda would be improved by strengthening institutional capacity and leadership and ensuring a transparent and participatory processes in which key stakeholders such as program implementers (the districts) and beneficiaries (the public) are
Safety, tolerability, and immunogenicity of 7-valent pneumococcal conjugate vaccine in older infants and young children in China who are naive to pneumococcal vaccination: Results of a phase 4 open-label trial.
Li, Rongcheng; Huang, Lirong; Mo, Shunping; Li, Junchun; Zhou, Xin; Chen, Zhangjing; Liang, John; Young, Mariano; Giardina, Peter C; Scott, Daniel A
This postlicensure study was conducted to assess immunogenicity and safety of PCV7 catch-up regimens in previously unvaccinated older infants and young children in China. Healthy children 121 days to vaccination and 1 and 12 months postvaccination. The incidence of clinically important adverse events (AEs) and serious AEs (SAEs), AEs leading to study withdrawal, and protocol-related AEs were assessed throughout the study. Prevaccination serotype-specific GMCs were generally low in subjects children 24 to 90% of subjects had IgG≥0.35 μg/mL for each PCV serotype. At 12-month follow-up, IgG GMCs ranged from 0.65 to 5.19, and all remained above prevaccination IgG GMC; >70% of subjects had IgG≥0.35 μg/mL. Older children generally had the most robust immune response both at 1 month postvaccination and during 12-month follow-up. PCV7 was well tolerated. Pyrexia, which was mild to moderate in severity, was the most common AE. Two subjects reported SAEs (n=4), and there was 1 study withdrawal; none of these were considered treatment related. In China, PCV7 catch-up vaccinations given to older infants and young children naive to pneumococcal vaccines resulted in a robust immune response to all serotypes; this response persisted after 1 year. PCV7 was well tolerated in Chinese infants and children. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Luciano Cesar Pontes Azevedo
Full Text Available Bacterial meningitis is associated with significant burden in Brazil. In 2010, both 10-valent pneumococcal conjugate vaccine and meningococcal capsular group C conjugate vaccine were introduced into the routine vaccination schedule. Haemophilus influenzae type b vaccine was previously introduced in 1999. This study presents trends in demographics, microbiological characteristics and seasonality patterns of bacterial meningitis cases in Brazil from 2000 to 2010.All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2000 and 2010 were analyzed. Proportions of bacterial meningitis cases by demographic characteristics, criteria used for confirmation and etiology were calculated. We estimated disease rates per 100,000 population and trends for the study period, with emphasis on H. influenzae, N. meningitidis and S. pneumoniae cases. In the decade, 341,805 cases of meningitis were notified in Brazil. Of the 251,853 cases with defined etiology, 110,264 (43.8% were due to bacterial meningitis (excluding tuberculosis. Of these, 34,997 (31.7% were due to meningococcal disease. The incidence of bacterial meningitis significantly decreased from 3.1/100,000 population in 2000-2002 to 2.14/100,000 in 2009-2010 (p<0.01. Among cases of meningococcal disease, the proportion of those associated with group C increased from 41% in 2007 to 61.7% in 2010, while the proportion of group B disease progressively declined. Throughout the study period, an increased number of cases occurred during winter.Despite the reduction in bacterial meningitis incidence during the last decade, it remains a significant healthcare issue in Brazil. Meningococcal disease is responsible for the majority of the cases with group C the most common capsular type. Our study demonstrates the appropriateness of introduction of meningococcal vaccination in Brazil. Furthermore, this study provides a baseline
Full Text Available Smoldering multiple myeloma (SMM is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM, a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM pre and post routine-vaccination with PCV13.Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA. The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month.At 1 month post vaccination, 12 patients (60% were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total of the 12 responders had persistent immunity, and only 2 (10% of total at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination.Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection. Keywords: Immunology, Vaccines, Infectious disease
Gargano, Lisa M; Hajjeh, Rana; Cookson, Susan T
Pneumonia is a leading cause of death among children less than five years old during humanitarian emergencies. Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae are the leading causes of bacterial pneumonia. Vaccines for both of these pathogens are available to prevent pneumonia. Problem This study describes an economic analysis from a publicly funded health care system perspective performed on a birth cohort in Somalia, a country that has experienced a protracted humanitarian emergency. An impact and cost-effectiveness analysis was performed comparing: no vaccine, Hib vaccine only, pneumococcal conjugate vaccine 10 (PCV10) only, and both together administered through supplemental immunization activities (SIAs). The main summary measure was the incremental cost per disability-adjusted life-years (DALYs) averted. One-way sensitivity analysis was conducted for uncertainty in parameter values. Each SIA would avert a substantial number of cases and deaths. Compared with no vaccine, the DALYs averted by two SIAs for two doses of Hib vaccine was US $202.93 (lower and upper limits: $121.80-$623.52), two doses of PCV10 was US $161.51 ($107.24-$227.21), and two doses of both vaccines was US $152.42 ($101.20-$214.42). Variables that influenced the cost-effectiveness for each strategy most substantially were vaccine effectiveness, case fatality rates (CFRs), and disease burden. The World Health Organization (WHO) defines a cost-effective intervention as costing one to three times the per capita gross domestic product (GDP; in 2011, for Somalia=US $112). Based on the presented model, Hib vaccine alone, PCV10 alone, or Hib vaccine and PCV10 given together in SIAs are cost-effective interventions in Somalia. The WHO/Strategic Advisory Group of Experts decision-making factors for vaccine deployment appear to have all been met: the disease burden is large, the vaccine-related risk is low, prevention in this setting is more feasible than treatment, the vaccine
Sasaki, Atsushi; Kunimoto, Masaru; Takeno, Sachio; Sumiya, Takahiro; Ishino, Takashi; Sugino, Hirotoshi; Hirakawa, Katsuhiro
This study investigated: (i) changes in the incidence of acute otitis media (AOM) following introduction of public funding for free inoculation with 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) and (ii) changes in the rate of myringotomies for AOM (MyfA) in children 1year following the publication of the first edition of the clinical practice guidelines for the diagnosis and management of AOM in children in Japan. PCV7 was launched on the Japanese market in 2010 and gained public funding in 2011. PCV7 was replaced with PCV13 in November 2013. Using the Japan Medical Data Center Claims Database, an 11-year study conducted between January 2005 and December 2015 investigated the decline in the incidence of visits to medical institutions (VtMI) due to all-cause AOM in children <15years. The rate of MyfA from January 2007 to December 2015was also investigated and changes before and after introduction of public funding for PCV7 (pfPCV7) and PCV13 (pfPCV13) for children were examined. Statistical data for the age group between 10 years and <15years served as the control. An analysis was conducted to examine changes for each age group, from infants that had received PCVs to children <5years. Statistical analysis was performed using the chi-square test and Ryan's multiple comparison tests. Ryan's multiple comparison tests were applied at a 5% level of significance. Due to significant changes in the guidelines on the indications for myringotomy introduced in 2013, statistical analysis of the rate of MyfA was limited to the pre- and post-PCV7 period. After introduction of pfPCV7 and pfPCV13, no significant suppression of the incidence of VtMI was observed in any age group. There was a gradual decline in the rate of MyfA after 2011. Compared to the control group, significant differences in all age groups from infants to children <5years were observed (p<0.009, chi-square test). Within 2 years after the introduction of PCV7, a significant
Jokinen, Jukka; Snellman, Marja; Palmu, Arto A; Saukkoriipi, Annika; Verlant, Vincent; Pascal, Thierry; Devaster, Jeanne-Marie; Hausdorff, William P; Kilpi, Terhi M
Clinical assessments of vaccines to prevent pneumococcal (Pnc) community-acquired pneumonia (CAP) require sensitive and specific case definitions, but there is no gold standard diagnostic test. To develop a new case definition suitable for vaccine efficacy studies, we applied latent class analysis (LCA) to the results from seven diagnostic tests for Pnc etiology on clinical specimens from 323 elderly radiologically-confirmed pneumonia cases enrolled in The Finnish Community-Acquired Pneumonia Epidemiology study during 2005-2007. Compared to the conventional use of LCA, which is mainly to determine sensitivities and specificities of different tests, we instead used LCA as an appropriate instrument to predict the probability of Pnc etiology for each CAP case based on their test profiles, and utilized the predictions to minimize the sample size that would be needed for a vaccine efficacy trial. When compared to the conventional laboratory criteria of encapsulated Pnc in blood culture or in high-quality sputum culture or urine antigen positivity, our optimized case definition for PncCAP resulted in a trial sample size which was almost 20,000 subjects smaller. We believe that our novel application of LCA detailed here to determine a case definition for PncCAP could also be similarly applied to other diseases without a gold standard. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
Jroundi, Imane; Mahraoui, Chafik; Benmessaoud, Rachid; Moraleda, Cinta; Munoz Almagro, Carmen; Seffar, Meryem; Tligui, Houssain; Kettani, Selma C; Benjelloun, Badr S; Alonso, Pedro L; Bassat, Quique
Nasopharyngeal carriage studies provide insights into the local prevalence of circulating pneumococcal serotypes. These data are critical to vaccination monitoring, as they allow for the prediction and assessment of impact. Very little data are available on the carriage of pneumococcal serotypes in Morocco. Here, we describe the prevalence of Streptococcus pneumoniae carriage and serotype distribution among 697 pediatric patients with ages ranging from 2 to 59 months who were admitted to a Moroccan hospital with severe pneumonia, as well as 195 healthy infants and young children who were recruited at a vaccination clinic. Carriage rates were 40.5% (79/195) for healthy children and 22.8% (159/697) for sick children. The most commonly observed circulating serotypes included 6A, 6B and 19F, all of which are included in the current 13-valent anti-pneumococcal conjugate vaccine that was recently introduced in Morocco. Monitoring of circulating serotypes remains necessary after vaccine introduction to assess whether serotype replacement is occurring. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
... the cause. In the case of pneumococcal disease, antibiotics can help prevent severe illness. Diagnosis If doctors suspect invasive ... In addition to the vaccine, appropriate use of antibiotics may also slow or reverse drug-resistant pneumococcal infections. Related Links ... Formats Help: How do I view different file formats (PDF, ...
Clark, Rebecca Culver; Carter, Kimberly Ferren; Jackson, Julie; Hodges, Deborah
The purpose of this quality improvement study was to explore the impact of audit and feedback on the pneumococcal immunization rate for at-risk adults in ambulatory settings. Study findings support the hypothesis that timely, individualized audit and feedback can have a positive impact on immunization rate; generalized feedback that did not provide actionable information did not have the same impact. The difference between the interventions was significant, χ (1, N = 1993) = 124.7, P <.001.
Full Text Available Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the "shaving" proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called "pan-surfome", consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141, whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms.
A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia.
Lim, Fong Seng; Koh, Mia Tuang; Tan, Kah Kee; Chan, Poh Chong; Chong, Chia Yin; Shung Yehudi, Yeo Wee; Teoh, Yee Leong; Shafi, Fakrudeen; Hezareh, Marjan; Swinnen, Kristien; Borys, Dorota
The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed. In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA. Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study. PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in
Bahuaud, Mathilde; Bodilis, Hélène; Malphettes, Marion; Maugard Landre, Anaïs; Matondo, Caroline; Bouscary, Didier; Batteux, Frédéric; Launay, Odile; Fermand, Jean-Paul
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA). The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month. At 1 month post vaccination, 12 patients (60%) were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total) of the 12 responders had persistent immunity, and only 2 (10% of total) at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination. Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection.
LeBlanc, Jason J; ElSherif, May; Ye, Lingyun; MacKinnon-Cameron, Donna; Li, Li; Ambrose, Ardith; Hatchette, Todd F; Lang, Amanda L; Gillis, Hayley; Martin, Irene; Andrew, Melissa K; Boivin, Guy; Bowie, William; Green, Karen; Johnstone, Jennie; Loeb, Mark; McCarthy, Anne; McGeer, Allison; Moraca, Sanela; Semret, Makeda; Stiver, Grant; Trottier, Sylvie; Valiquette, Louis; Webster, Duncan; McNeil, Shelly A
Pneumococcal community acquired pneumonia (CAP Spn ) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes. Active surveillance for CAP Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay. In total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP Spn . Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized
Qiu, Y P; Zhao, K; Li, X; Shi, L W; Guo, W D; Qi, X R; Sui, B Y; Zhou, R M
Objective: From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods: In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results: By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient treatments and 0.85±1.15 hospitalizations
Full Text Available Abstract Background In many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV-23 is recommended to prevent pneumococcal disease in the elderly. However, vaccine-induced immunity wanes after a few years, and there are controversies around revaccination with PPSV-23. Here, we systematically assessed the effectiveness and safety of PPSV-23 revaccination. Method We conducted a systematic literature review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to June 2015. We included all study types that compared effectiveness, immunogenicity and/or safety of PPSV-23 as a primary vs. a revaccination dose in persons aged 50 years and older. With respect to immunogenicity, we calculated the ratio of geometric mean antibody concentrations and opsonophagocytic indexes at identical time-points after primary and revaccination. Additionally, we compared rates and severity of adverse events (AEs after primary and revaccination. Results We included 14 observational studies. 10 studies had a prospective design and analysed data on (i the same individuals after a first and a second dose of PPSV-23 given 1 to 10 years later (n = 5 or (ii two groups consisting of participants receiving PPSV-23 who were either vaccine-naïve or had received a first PPSV-23 dose 3 to 13 years earlier (n = 5. Three studies used electronic data bases to compare AEs after primary vs. revaccination doses of PPSV-23 after 1 to 10 years and one study had a cross-sectional design. Number of participants in the non-register-based and register-based studies ranged from 29 to 1414 and 360 to 316,000, respectively. 11 out of 14 included studies were at high risk of bias, three studies had an unclear risk of bias. None of the studies reported data on clinical effectiveness. Immunogenicity studies revealed that during the first two months antibody levels tended to be lower after revaccination as compared to
Carpenter, Ryan M; Limb, Charles J; Francis, Howard W; Gottschalk, Barbara; Niparko, John K
Bacterial meningitis represents a substantial concern for individuals with cochlear implants (CIs). Chart review and direct patient and family correspondence to ascertain vaccination status. Information dissemination via brochure and electronic media, ongoing reminders of the importance of vaccination when confirmation of vaccination was not received. Marked improvement in vaccination rates ranging from 49% to 99% across different patient populations. Importantly, many patients received their vaccinations only after follow-up reminders. Ensuring optimal vaccination of all CI recipients against high-risk pathogens is a significantly challenging task. Maximizing vaccination rates in CI users will require an ongoing, active effort of information dissemination, documentation of compliance, and well-designed behavioral systems to streamline the pragmatic challenges in vaccination delivery.
Full Text Available Abstract Background Medical and public health importance of pneumococcal infections justifies the implementation of measures capable of reducing their incidence and severity, and explains why the recently marketed heptavalent pneumococcal conjugate vaccine (PCV-7 has been widely studied by pediatricians. This study was designed to evaluate the impact of PCV-7 administered at 3, 5 and 11 months of age on respiratory tract infections in very young children. Methods A total of 1,571 healthy infants (910 males aged 75–105 days (median 82 days were enrolled in this prospective cohort trial to receive a hexavalent vaccine (DTaP/IPV/HBV/Hib and PCV-7 (n = 819 or the hexavalent vaccine alone (n = 752 at 3, 5 and 11 months of age. Morbidity was recorded for the 24 months following the second dose by monthly telephone interviews conducted by investigators blinded to the study treatment assignment using standardised questionnaires. During these interviews, the caregivers and the children's pediatricians were questioned about illnesses and the use of antibiotics since the previous telephone call. All of the data were analysed using SAS Windows v.12. Results Among the 1,555 subjects (98.9% who completed the study, analysis of the data by the periods of follow-up demonstrated that radiologically confirmed community-acquired pneumonia (CAP was significantly less frequent in the PCV-7 group during the follow-up as a whole and during the last period of follow-up. Moreover, there were statistically significant between-group differences in the incidence of acute otitis media (AOM in each half-year period of follow-up except the first, with significantly lower number of episodes in children receiving PCV-7 than in controls. Furthermore, the antibiotic prescription data showed that the probability of receiving an antibiotic course was significantly lower in the PCV-7 group than in the control group. Conclusion Our findings show the effectiveness of the simplified
Silfverdal, Sven Arne; Høgh, Birthe; Bergsaker, Marianne Riise
BACKGROUND: The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. METHODS: A total of 351 healthy....... RESULTS: Depending on the serotype, the percentages of subjects reaching the ELISA antibody threshold of 0.2 microg/mL were 92.8% to 98.0% following 2 primary doses and 96.1% to 100% following 3 primary doses except for serotype 6B (55.7% and 63.1%, respectively) and serotype 23F (69.3% and 77...
Kedibone M Ndlangisa
Full Text Available We determined the sequence types of isolates that caused invasive pneumococcal disease (IPD prior to routine use of pneumococcal conjugate vaccines (PCV in South Africa. PCV-13 serotypes and 6C isolates collected in 2007 (1 461/2 437, 60% from patients of all ages as part of on-going, national, laboratory-based surveillance for IPD, were selected for genetic characterization. In addition, all 134 non-PCV isolates from children <2 years were selected for characterization. Sequence type diversity by serotype and age category (children <5 years vs. individuals ≥5 years was assessed for PCV serotypes using Simpson's index of diversity. Similar genotypes circulated among isolates from children and adults and the majority of serotypes were heterogeneous. While globally disseminated clones were common among some serotypes (e.g., serotype 1 [clonal complex (CC 217, 98% of all serotype 1] and 14 [CC230, 43%], some were represented mainly by clonal complexes rarely reported elsewhere (e.g., serotype 3 [CC458, 60%] and 19A [CC2062, 83%]. In children <2 years, serotype 15B and 8 were the most common serotypes among non-PCV isolates (16% [22/134] and 15% [20/134] isolates, respectively. Sequence type 7052 and 53 were most common among serotypes 15B and 8 isolates and accounted for 58% (7/12 and 64% (9/14 of the isolates, respectively. Serotype 19F, 14, 19A and 15B had the highest proportions of penicillin non-susceptible isolates. Genotypes rarely reported in other parts of the world but common among some of our serotypes highlight the importance of our data as these genotypes may emerge post PCV introduction.
Full Text Available Abstract Background The 23-valent polysaccharide pneumococcal vaccine (PPV-23 is recommended for elderly and high-risk people, although its effectiveness is controversial. Some studies have reported an increasing risk of acute vascular events among patients with pneumonia, and a recent case-control study has reported a reduction in the risk of myocardial infarction among patients vaccinated with PPV-23. Given that animal experiments have shown that pneumococcal vaccination reduces the extent of atherosclerotic lesions, it has been hypothesized that PPV-23 could protect against acute vascular events by an indirect effect preventing pneumonia or by a direct effect on oxidized low-density lipoproteins. The main objective of this study is to evaluate the clinical effectiveness of PPV-23 in reducing the risk of pneumonia and acute vascular events (related or nonrelated with prior pneumonia in the general population over 60 years. Methods/Design Cohort study including 27,000 individuals 60 years or older assigned to nine Primary Care Centers in the region of Tarragona, Spain. According to the reception of PPV-23 before the start of the study, the study population will be divided into vaccinated and nonvaccinated groups, which will be followed during a consecutive 30-month period. Primary Care and Hospitals discharge databases will initially be used to identify study events (community-acquired pneumonia, hospitalisation for acute myocardial infarction and stroke, but all cases will be further validated by checking clinical records. Multivariable Cox regression analyses estimating hazard ratios (adjusted for age, sex and comorbidities will be used to estimate vaccine effectiveness. Discussion The results of the study will contribute to clarify the controversial effect of the PPV-23 in preventing community-acquired pneumonia and they will be critical in determining the posible role of pneumococcal vaccination in cardiovascular prevention.
Delgleize, Emmanuelle; Leeuwenkamp, Oscar; Theodorou, Eleni; Van de Velde, Nicolas
In 2010, the 13-valent pneumococcal conjugate vaccine (PCV-13) replaced the 7-valent vaccine (introduced in 2006) for vaccination against invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) in the UK. Using recent evidence on the impact of PCVs and epidemiological changes in the UK, we performed a cost-effectiveness analysis (CEA) to compare the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with PCV-13 in the ongoing national vaccination programme. CEA was based on a published Markov model. The base-case scenario accounted only for direct medical costs. Work days lost were considered in alternative scenarios. Calculations were based on serotype and disease-specific vaccine efficacies, serotype distributions and UK incidence rates and medical costs. Health benefits and costs related to IPD, pneumonia and AOM were accumulated over the lifetime of a UK birth cohort. Vaccination of infants at 2, 4 and 12 months with PHiD-CV or PCV-13, assuming complete coverage and adherence. The incremental cost-effectiveness ratio (ICER) was computed by dividing the difference in costs between the programmes by the difference in quality-adjusted life-years (QALY). Under our model assumptions, both vaccines had a similar impact on IPD and pneumonia, but PHiD-CV generated a greater reduction in AOM cases (161 918), AOM-related general practitioner consultations (31 070) and tympanostomy tube placements (2399). At price parity, PHiD-CV vaccination was dominant over PCV-13, saving 734 QALYs as well as £3.68 million to the National Health Service (NHS). At the lower list price of PHiD-CV, the cost-savings would increase to £45.77 million. This model projected that PHiD-CV would provide both incremental health benefits and cost-savings compared with PCV-13 at price parity. Using PHiD-CV could result in substantial budget savings to the NHS. These savings could be used to implement other life-saving interventions
Diez-Domingo, Javier; Gurtman, Alejandra; Bernaola, Enrique; Gimenez-Sanchez, Francisco; Martinon-Torres, Federico; Pineda-Solas, Valentin; Delgado, Alfonso; Infante-Marquez, Pilar; Liang, John Z; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A
Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing
Chatham, W; Chadha, A; Fettiplace, J; Kleoudis, C; Bass, D; Roth, D; Gordon, D
Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11-23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little
VACCINE IMMUNIZATION FOR PREVENTION OF PNEUMOCOCCAL, HAEMOPHILUS INFLUENZAE AND FLU AMONG SICKLY CHILDREN, WHO OFTEN SUFFER FROM PERSISTENT HETEROSPECIFIC INFECTIOUS PATHOLOGY OF THE BRONCHOPULMONARY SYSTEM
Full Text Available Among serious diseases of the lower respiratory tract a special place is taken by pneumonias and chronic infectious respiratory diseases caused by pneumococcus and Haemophilus influenzae type b (HIB. The research purpose is to determine the effectiveness of vaccine combined application to treat sickly children, who often suffer from persistent infectious pathology of the respiratory tract, for flu, pneumococcal and HIB disease. 110 children aged between 3 and 12 have been vaccinated. The first part of research implied children vaccination by means of Actahib and Pneumo 23 vaccines (Sanofi Pasteur, France, the second one consisted in immunization of children with the same pathology by means of Pneumo 23, Actahib and Vaxigrip vaccines (Sanofi Pasteur, France. The researches established that within a year after HIB and Pneumo 23 vaccination the frequency of upper and lower respiratory tract acerbations reduced by 2,3 times on average; likewise, the number of system antimicrobial dosage reduced by 7,4 times along with the total duration of dosage; the carrier state of S. pneumoniae reduced by 3,7 times, H. influenzae — by 3,9 times. In the course of application of three vaccines, the frequency of persistent heat erospecific infectious bronchopulmonary pathology acerbations reduced by 3,3 times. The carrier state of S. pneumoniae reduced by 2,5 times, H. influenzae — by 4,1 times. Thus, vaccine immunization to treat for flu, pneumococcal and HIB disease in various combinations may be recoma mended for wider application to reduce the frequency and severity of heat erospecific infectious respiratory diseases among sickly children, who often suffer from various illnesses.Key words: children with recurrent diseases, vaccination, prevention, flu, H. Influenzae, S. pneumoniae.
Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M
Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and
Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age.
Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray
The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.15 μg/ml, PCV serotype-specific IgG concentrations of ≥0.35 μg/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ≥11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.
Full Text Available The article is dedicated to the actual problem of modern health care — pneumococcal infections and opportunities of its prophylaxis. Authors describe risk groups of development of invasive pneumococcal infections. A characteristics of available at the present times in Russia and all over the world vaccines, including pneumococcal 7-valent vaccine (PCV7 Prevenar, intended to the prophylaxis of pneumococcal infections in children under the age 2 months — 5 years old. An experience of PCV7 use in the world in analyzed. The article gives an estimation of perspectives of inclusion of PCV7 to the national immunizations schedule.Key words: children, pneumococcal infections, prophylaxis, pneumococcal conjugated 7-valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:62-69
Benfield, Thomas Lars Vibe; Skovgaard, Marlene; Schønheyder, Henrik Carl
There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP).......There is limited knowledge of serotypes that cause non-bacteremic pneumococcal pneumonia (NBP). Here we report serotypes, their associated disease potential and coverage of pneumococcal conjugate vaccines (PCV) in adults with NBP and compare these to bacteremic pneumonia (BP)....
Epidemiology of Otitis Media with Spontaneous Perforation of the Tympanic Membrane in Young Children and Association with Bacterial Nasopharyngeal Carriage, Recurrences and Pneumococcal Vaccination in Catalonia, Spain - The Prospective HERMES Study.
Cilveti, Robert; Olmo, Montserrat; Pérez-Jove, Josefa; Picazo, Juan-José; Arimany, Josep-Lluis; Mora, Emiliano; Pérez-Porcuna, Tomás M; Aguilar, Ignacio; Alonso, Aurora; Molina, Francesc; Del Amo, María; Mendez, Cristina
The Epidemiology of otitis media with spontaneous perforation of the tympanic membrane and associated nasopharyngeal carriage of bacterial otopathogens was analysed in a county in Catalonia (Spain) with pneumococcal conjugate vaccines (PCVs) not included in the immunization programme at study time. A prospective, multicentre study was performed in 10 primary care centres and 2 hospitals (June 2011-June 2014), including all otherwise healthy children ≥2 months ≤8 years with otitis media presenting spontaneous tympanic perforation within 48h. Up to 521 otitis episodes in 487 children were included, showing by culture/PCR in middle ear fluid (MEF): Haemophilus influenzae [24.2%], both Streptococcus pneumoniae and H. influenzae [24.0%], S. pneumoniae [15.9%], Streptococcus pyogenes [13.6%], and Staphylococcus aureus [6.7%]. Culture-negative/PCR-positive otitis accounted for 31.3% (S. pneumoniae), 30.2% (H. influenzae) and 89.6% (mixed S. pneumoniae/H. influenzae infections). Overall, incidence decreased over the 3-year study period, with significant decreases in otitis by S. pneumoniae and by H. influenzae, but no decreases for mixed S. pneumoniae/H. influenzae infections. Concordance between species in nasopharynx and MEF was found in 58.3% of cases, with maximal rates for S. pyogenes (71.8%), and with identical pneumococcal serotype in 40.5% of cases. Most patients (66.6%) had past episodes. PCV13 serotypes were significantly more frequent in first episodes, in otitis by S. pneumoniae as single agent, and among MEF than nasopharyngeal isolates. All non-PCV13 serotypes separately accounted for <5% in MEF. Up to 73.9% children had received ≥1 dose of PCV, with lower carriage of PCV13 serotypes than among non-vaccinated children. Pooling pneumococcal isolates from MEF and nasopharynx, 30% were multidrug resistant, primarily belonging to serotypes 19A [29.8%], 24A [14.3%], 19F [8.3%] and 15A [6.0%]. Our results suggest that increasing PCV13 vaccination would
Epidemiology of Otitis Media with Spontaneous Perforation of the Tympanic Membrane in Young Children and Association with Bacterial Nasopharyngeal Carriage, Recurrences and Pneumococcal Vaccination in Catalonia, Spain - The Prospective HERMES Study.
Full Text Available The Epidemiology of otitis media with spontaneous perforation of the tympanic membrane and associated nasopharyngeal carriage of bacterial otopathogens was analysed in a county in Catalonia (Spain with pneumococcal conjugate vaccines (PCVs not included in the immunization programme at study time. A prospective, multicentre study was performed in 10 primary care centres and 2 hospitals (June 2011-June 2014, including all otherwise healthy children ≥2 months ≤8 years with otitis media presenting spontaneous tympanic perforation within 48h. Up to 521 otitis episodes in 487 children were included, showing by culture/PCR in middle ear fluid (MEF: Haemophilus influenzae [24.2%], both Streptococcus pneumoniae and H. influenzae [24.0%], S. pneumoniae [15.9%], Streptococcus pyogenes [13.6%], and Staphylococcus aureus [6.7%]. Culture-negative/PCR-positive otitis accounted for 31.3% (S. pneumoniae, 30.2% (H. influenzae and 89.6% (mixed S. pneumoniae/H. influenzae infections. Overall, incidence decreased over the 3-year study period, with significant decreases in otitis by S. pneumoniae and by H. influenzae, but no decreases for mixed S. pneumoniae/H. influenzae infections. Concordance between species in nasopharynx and MEF was found in 58.3% of cases, with maximal rates for S. pyogenes (71.8%, and with identical pneumococcal serotype in 40.5% of cases. Most patients (66.6% had past episodes. PCV13 serotypes were significantly more frequent in first episodes, in otitis by S. pneumoniae as single agent, and among MEF than nasopharyngeal isolates. All non-PCV13 serotypes separately accounted for <5% in MEF. Up to 73.9% children had received ≥1 dose of PCV, with lower carriage of PCV13 serotypes than among non-vaccinated children. Pooling pneumococcal isolates from MEF and nasopharynx, 30% were multidrug resistant, primarily belonging to serotypes 19A [29.8%], 24A [14.3%], 19F [8.3%] and 15A [6.0%]. Our results suggest that increasing PCV13 vaccination
Lehmann, Birthe A; Eilers, Renske; Mollema, Liesbeth; Ferreira, José; de Melker, Hester E
Increasing life expectancy results in a larger proportion of older people susceptible to vaccine preventable diseases (VPDs). In the Netherlands, influenza vaccination is routinely offered to people aged 60 years and older. Vaccination against pneumococcal disease, herpes zoster and pertussis is rarely used. These vaccines will be evaluated by the Dutch Health Council and might be routinely offered to older people in the near future. Possible expansion of the program depends partly on the willingness of general practitioners (GPs) to endorse additional vaccinations. In this study, we assessed predictors of GPs' attitude and intention to vaccinate people aged 60 years and older. GPs (N = 12.194) were invited to fill in an online questionnaire consisting of questions about social cognitive factors that can influence the willingness of GPs to vaccinate people aged 60 years and older, including underlying beliefs, practical considerations of adding more vaccines to the national program, demographics, and GPs' patient population characteristics. The questionnaire was filled in by 732 GPs. GPs were positive both about vaccination as a preventive tool and the influenza vaccination program, but somewhat less positive about expanding the current program. Prediction analysis showed that the intention of GPs to offer additional vaccination was predicted by their attitude towards offering additional vaccination, towards vaccination as a preventive tool, towards offering vaccination during an outbreak and on GPs opinion regarding suitability to offer additional vaccination (R 2 = 0.60). The attitude of GPs towards offering additional vaccination was predicted by the perceived severity of herpes zoster and pneumonia, as well as the perceived incidence of herpes zoster. Severity of diseases was ranked as important argument to recommend vaccination, followed by effectiveness and health benefits of vaccines. Providing GPs with evidence-based information about the severity
Doyle, D M; Dauterive, R; Chuang, K H; Ellrodt, A G
There are many challenges to effectively and efficiently translating evidence into practice. Potential strategies include (1) training more evidence-based practitioners in the art and science of evidence-based medicine, (2) enhancing the quality and availability of systematic reviews, and (3) more effectively linking evidence-based practitioners and evidence users through comprehensive behavioral change initiatives. Herein we explore the third strategy and highlight the key elements of success for a program using behavioral change strategies. We present a clinical model based on clear understanding of the "problem," a systematic approach to diagnosis, selection of scientifically sound treatment options, and effective evaluation with appropriate modification of the treatment plan. A successful program begins with effective team leadership, the expression of a clinically compelling case for change, and commitment to the pursuit of perfection in the delivery of key evidence-based interventions. The team must then diagnose behavioral barriers to change, using a systematic approach based on a published rigorous differential diagnosis framework. This diagnostic step provides the foundation for selection of effective dissemination and implementation strategies (treatments) proven to improve processes of care and clinical outcomes. Finally the team must evaluate progress toward perfection, reviewing interim data and adjusting the treatment regimen to newly diagnosed barriers. We then present a specific project (improving pneumococcal immunization rates in our rural community) and interim results to demonstrate the use of the framework in the real world.
Gargano, Lisa M; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S; Pazol, Karen; Bahl, Sunil; Jafari, Hamid S; Arora, Manisha; Orenstein, Walter A; Hughes, James M; Omer, Saad B
According to the World Health Organization in 2008, pneumonia accounted for 20% of deaths and diarrheal diseases accounted for 13% of deaths among children under 5 in India. Vaccines are available for Streptococcus pneumoniae (pneumococcal conjugate vaccine (PCV)), Haemophilus influenzae type b (Hib vaccine), and rotavirus. Barriers to including these vaccines in routine immunization schedule in India include potential negative impacts on fragile existing immunization programs and cost. Pediatricians who are members of the Indian Academy of Pediatrics (IAP) are important stakeholders for vaccine delivery and maintaining public confidence in vaccines. A random sample of 785 pediatricians belonging to IAP was selected for the survey conducted from June 2009 to June 2010. Descriptive analyses using sampling weights were performed to evaluate the distributions of variables assessing vaccine-related attitudes and behaviors among pediatricians. Logistic regression was used to assess factors associated with routine vaccine use. The majority of pediatricians reported administering PCV (85.6%), Hib (95.9%), and rotavirus (80.2%) vaccine selectively or routinely. Pediatricians who had high perceived disease susceptibility were 2.42 times more likely to report routine administration of Hib vaccine (OR 2.42, 95% CI 1.24, 4.74). Pediatricians who had high perceived Hib vaccine efficacy were 4.74 times more likely to administer Hib vaccine routinely (OR 4.74, 95% CI 2.09, 10.74). Perceptions of disease susceptibility and severity or of vaccine safety and efficacy were not associated with routine administration of PCV or rotavirus vaccine. Understanding predictors of routine use of a new vaccine could help focus interventions to improve the routine use of other vaccines. The importance of perceived susceptibility to and severity of diseases caused by S. pneumoniae, Hib, and rotavirus and perceived efficacy and safety of the vaccines by pediatricians presents an opportunity to
Pineda Solas, V; Pérez Benito, A; Domingo Puiggros, M; Larramona Carrera, H; Segura Porta, F; Fontanals Aymerich, D
Streptococcus pneumonia is the most common bacterial cause of community-acquired pneumonia in children. The reference standard for etiological diagnosis is isolation of S. pneumoniae from blood Since the advent of conjugate vaccines, disease caused by this organism can now be prevented. Many studies have been performed of the global incidence of invasive pneumococcal infections and of pneumococcal meningitis but few studies investigated bacteremic pneumococcal pneumonia and its complications in children. To determine the incidence, patient characteristics, clinical signs, laboratory data, percentage and days of hospitalization, response to antibiotic treatment, antibiotic resistance, complications and causal serogroups of bacteremic pneumococcal pneumonia in our environment in order to estimate requirements for systematic vaccination programs. From January 1990 to May 2001, data on all pediatric cases of invasive pneumococcal infections diagnosed in our hospital were collected. Several characteristics of patients with bacteremic pneumococcal pneumonia were analyzed. Bacteremic pneumococcal pneumonia was diagnosed in patients with positive blood or pleural fluid cultures for S. pneumoniae and radiographically evident pulmonary infiltrate. The incidence of both types of pneumonia were determined according to population census data. All S. pneumonia strains were sent to the Pneumococci Reference Laboratory of the Instituto Carlos III in Madrid for serotyping. We estimated the serotype coverage of the pneumococcal 7-valent conjugate vaccine according to the serotypes included in this vaccine and their distribution. Forty cases of bacteremic pneumococcal pneumonia were diagnosed, yielding an incidence of 17,10 and 5 cases per 10(5) children aged less than 2, 4 and 15 years old respectively. The mean age was 50 months and 43% were aged less than 4 years. Peaks occurred in January, March, April and May. A total of 77.5% of the patients were admitted to hospital and the
Many causes can be proposed for a change in the microbiologic makeup of a specific disease state. However, when viewed through the scope of recent events, only one is likely to be the true cause of a change in the microbiology of acute otitis media (AOM): the release and widespread use of heptavalent pneumococcal conjugate vaccine (PCV-7). The aim of this report was to review the microbiology and prevalence of AOM before and after the release and widespread use of PCV-7. For this brief review, we used a MEDLINE search to identify English-language literature related to the microbiology of AOM before and after the release of PCV-7 in 2000 in the United States (key terms: acute otitis media, AOM, Haemophilus influenzae, H influenzae, Streptococcus pneumoniae, and S pneumoniae; years: 1980-2005). Studies using tympanocentesis to identify the pathogen in recurrent or persistent AOM were examined; US studies reporting AOM microbiology before and after the release of PCV-7 in the same population were considered for the post-PCV-7 analysis. Following the release of PCV-7, a decrease in the overall rates of AOM was noted. This decrease brings into question the resultant effect on the microbiology of AOM. Our literature search revealed 2 studies that examined the microbiology of AOM before and after the release of PCV-7 in the United States. These 2 studies, conducted in dispersed geographic regions (rural Kentucky and Rochester, New York), illustrated a change in the predominant causative pathogen in AOM, from S pneumoniae to H influenzae in the population of children 7 to 24 months of age with recurrent AOM. Given the time period of the change, these shifts could be related to the release and widespread use of PCV-7. Since the 1990s, the predominant causative pathogen in recurrent AOM changed from S pneumoniae to H influenzae, possibly as a result of the release and widespread use of PCV 7. Although PCV-7 use was slowed from August 2001 to May 2003 and again from February
Cremers, Amelieke J H; Mobegi, Fredrick M; de Jonge, Marien I; van Hijum, Sacha A F T; Meis, Jacques F; Hermans, Peter W M; Ferwerda, Gerben; Bentley, Stephen D; Zomer, Aldert L
The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped
Irma Gabriela Echániz-Avilés
Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.htmlStreptococcus pneumoniae es uno de los principales agentes causantes de enfermedades invasoras y no invasoras en la población pediátrica y sigue representando uno de los principales problemas de salud pública a nivel mundial. La incidencia creciente de cepas resistentes a diversos antimicrobianos ha complicado el tratamiento y manejo de varias de las manifestaciones de la enfermedad neumocócica. Con éstas consideraciones, la mejor estrategia de manejo es la prevención de éstas enfermedades a través de la vacunación. A pesar de que se han estudiado diversas vacunas neumocócicas conjugadas en niños, solo una
Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.
Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota
This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.
Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.
Szenborn, L; Osipova, I V; Czajka, H; Kharit, S M; Jackowska, T; François, N; Habib, M A; Borys, D
Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. PHiD-CV was immunogenic and well tolerated in 2
Full Text Available THE AIM OF THE RESEARCH WAS TO ASSESS THE CLINIC EFFECTIVENESS OF A COMBINED APPLICATION OF SUCH VACCINES AS: ACTBHIB AND PNEUMO 23 (SANOFI PASTEUR, FRANCE IN CHILDREN, WHO ARE PRONE TO FREQUENT AND PROLONGED RECURRENT OTITES MEDIA. DURING 2004 AND 2005, 153 CHILDREN AGED BETWEEN 2 AND 12 YEARS OLD WERE IMMUNIZED AND OBSERVED. THE CONTROL GROUP WAS MADE UP OF 30 CHILDREN, WHOSE PARENTS REFUSED TO PARTICIPATE IN VACCINATION. THE CHILDREN OF BOTH GROUPS WERE COMPARABLE. THE FINDINGS OF THE RESEARCH SHOWED HIGH PREVENTIVE EFFECTIVENESS OF THE COMBINED IMMUNIZATION, WHICH PROVIDED A 3BFOLD REDUCTION OF ACUTE RESPIRATORY INFECTIONS AND RECURRENT OTITES, A REDUCTION OF ANTIBACTERIAL THERAPY PRESCRIPTION BY MORE THAN 8 TIMES AND A REDUCTION OF H. INFLUENZAE AND PNEUMOCOCCUS CARRIAGE BY 9 TIMES. IN THE GROUP OF IMMUNIZED CHILDREN, THE RESEARCHERS OBSERVED A REDUCTION OF ADENOID VEGETATION AUXESIS, RECOVERY OF AUDITORY TUBE PASSABILITY IN 85% OF CASES ALONG WITH THE PRESSURE NORMALIZATION IN TYMPANIC CAVITY. THEREFORE, THESE FINDINGS ALLOW TO EXPAND INDICATIONS FOR THE COMBINED IMMUNIZATION BY VACCINES AGAINST HIBB AND PNEUMOCOCCAL INFECTION, AS WELL AS TO PURSUE IMMUNIZATION WITH PNEUMO 23 AND ACT-HIB VACCINES BY PNEUMO 23 AND ACTBHIB IN CHILDREN, WHO ARE PRONE TO FREQUENT AND PROLONGED RECURRENT OTITES MEDIA AND ADENOID VEGETATION AUXESIS.KEY WORDS: VACCINATION, CHILDREN, H. INFLUENZAE, S. PNEUMONIAE, OTITES MEDIA.
Miguel W Tregnaghi
Full Text Available The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP and acute otitis media (AOM is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV on these end points. The primary objective was to demonstrate vaccine efficacy (VE in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml; other protocol-specified outcomes were also assessed.This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201, per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002 against B-CAP (conclusive for primary objective and 25.7% (95% CI: 8.4%, 39.6% against World Health Organization-defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1% against B-CAP and 23.4% (95% CI: 8.8%, 35.7% against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease (IPD (PHiD-CV, n = 10,211; control, n = 10,140 and AOM (n = 3,010 and 2,979, respectively. Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032 against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9% against vaccine serotype clinically
Burton, Deron C.; Bigogo, Godfrey M.; Audi, Allan O.; Williamson, John; Munge, Kenneth; Wafula, Jackline; Ouma, Dominic; Khagayi, Sammy; Mugoya, Isaac; Mburu, James; Muema, Shadrack; Bauni, Evasius; Bwanaali, Tahreni; Feikin, Daniel R.; Ochieng, Peter M.; Mogeni, Ondari D.; Otieno, George A.; Olack, Beatrice; Kamau, Tatu; Van Dyke, Melissa K.; Chen, Robert; Farrington, Paddy; Montgomery, Joel M.; Breiman, Robert F.; Scott, J. Anthony G.; Laserson, Kayla F.
There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37–4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12–8.56) and 0.27 (95% CI 0.14–0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study. PMID:26509274
Harjaningrum, Agnes Tri; Kartasasmita, Cissy; Orne-Gliemann, Joanna; Jutand, Marthe-Aline; Goujon, Nicolas; Koeck, Jean-Louis
Due to the high burden of pneumonia in Indonesia, the inclusion of pneumococcal conjugate vaccine (PCV) into Indonesia's National Immunization Program (NIP) is recommended by World Health Organization. Prior to the introduction of new vaccines, it is imperative to assess the perceptions of the public and medical community about the disease and the vaccine. The purpose of this qualitative study was to explore the knowledge, perceptions, and attitudes of mothers and health care providers (HCPs) toward PCV in Bandung, West Java, Indonesia. Fifty-five respondents (26 mothers and 29 HCPs) were interviewed at public and private health care facilities in Bandung using semi-structured interviews in May-June 2011. Data were analyzed manually according to pre-defined themes. Although most mothers had low knowledge about PCV, did not perceive themselves as susceptible to the disease, perceived that cost was the main barrier to PCV access, and obtained little information on PCV, they considered pneumonia as a severe disease and a priority health problem, perceived benefits of the vaccine, and were likely to adopt it. Similarly, knowledge about PCV among most HCPs was limited. Despite perceiving cost as the main barrier, most HCPs perceived benefits of the vaccine, susceptibility and severity of the disease, regarded pneumonia as a priority health problem, and were likely to suggest the new vaccination. Despite the poor knowledge of mothers and HCPs about PCV, they are aware of the high burden of pneumonia and the need for a vaccine in the NIP. Perceived severity and benefits among mothers, and, additionally, perceived susceptibility among HCPs were manifested in the willingness to accept PCV. The findings would contribute to better understanding the factors, which could support decision-making about vaccine introduction, and be utilized for developing suitable messages for mothers and HCPs. Copyright © 2013 Elsevier Ltd. All rights reserved.
Alienke J Wijmenga-Monsuur
Full Text Available Since 2009/10, a 10- and a 13-valent pneumococcal conjugate vaccine (PCV are available, but only the 10-valent vaccine is now being used for the children in the Netherlands. As the vaccines differ in number of serotypes, antigen concentration, and carrier proteins this study was designed to directly compare quantity and quality of the antibody responses induced by PCV10 and PCV13 before and after the 11-month booster.Dutch infants (n = 132 were immunized with either PCV10 or PCV13 and DTaP-IPV-Hib-HepB at the age of 2, 3, 4 and 11 months. Blood samples were collected pre-booster and post-booster at one week and one month post-booster for quantitative and qualitative immunogenicity against 13 pneumococcal serotypes, as well as quantitative immunogenicity against diphtheria, tetanus, pertussis and Haemophilus influenzae type b. We compared immunogenicity induced by PCV13 and PCV10 for their ten shared serotypes.One month post-booster, pneumococcal serotype-specific IgG geometric mean concentrations (GMCs for the PCV13 group were higher compared with the PCV10 group for six serotypes, although avidity was lower. Serotype 19F showed the most distinct difference in IgG and, in contrast to other serotypes, its avidity was higher in the PCV13 group. One week post-booster, opsonophagocytosis for serotype 19F did not differ significantly between the PCV10- and the PCV13 group.Both PCV10 and PCV13 were immunogenic and induced a booster response. Compared to the PCV10 group, the PCV13 group showed higher levels for serotype 19F GMCs and avidity, pre- as well as post-booster, although opsonophagocytosis did not differ significantly between groups. In our study, avidity is not correlated to opsonophagocytotic activity (OPA and correlations between IgG and OPA differ per serotype. Therefore, besides assays to determine IgG GMCs, assays to detect opsonophagocytotic activity, i.e., the actual killing of the pneumococcus, are important for PCV evaluation. How
Tregnaghi, Miguel W.; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejón, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P.; Borys, Dorota; Guiñazú, Javier Ruiz; Ortega-Barría, Eduardo; Yarzábal, Juan P.; Schuerman, Lode
Background The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. Methods and Findings This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: −1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM
Kupek, Emil; Vieira, Ilse Lisiane Viertel
The aim of this study was to evaluate the impact of PCV10 pneumococcal vaccine on mortality from pneumonia in children less than one year of age in Santa Catarina State, Brazil, comparing the four years prior and the four years subsequent to the vaccine's introduction in 2010. This ecological study used data from the Mortality Information System and vaccination coverage of children less than one year. Data were grouped by municipalities of residence and regions. Average mortality from pneumonia in children under one year decreased from 29.69 to 23.40 per 100,000, comparing 2006-2009 and 2010-2013, or a reduction of 11%. However there were differences between regions with a drop in mortality (Grande Florianópolis, Sul, Planalto Norte, and Nordeste) and others with an increase in the annual rates (Oeste, Itajaí, and Serra). In short, the state as a whole showed 11% reduction in mortality from pneumonia in children less than one year of age, four years after implementing routine PCV10 vaccination in the National Immunization Program, but with heterogeneous effects when comparing regions of the state.
Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.
Thompson, Allison; Gurtman, Alejandra; Patterson, Scott; Juergens, Christine; Laudat, France; Emini, Emilio A; Gruber, William C; Scott, Daniel A
Meta-analyses enable summarization and interpretation of data across clinical trials. When applied to safety data they allow for detection of rare events. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was approved in multiple countries worldwide for routine immunization of infants and young children. This meta-analysis was conducted to identify potentially clinically important rare safety events associated with PCV13. To summarize the safety of PCV13 compared with 7-valent pneumococcal conjugate vaccine (PCV7) administered to infants and toddlers. A meta-analysis was performed of integrated safety data from 13 infant studies (PCV13 n=4729 and PCV7 n=2760) conducted in 9 North American, European, and Asian countries. Local reactions at the vaccine injection site and systemic events were collected for 4-7 days after each dose into electronic diaries. Adverse events (AEs) were collected after each vaccination. Overall, rates of local reactions after any dose of the infant series were similar between PCV13 and PCV7 groups: tenderness (46.7% vs 44.8%, respectively); swelling (28.5% vs 26.9%); and redness (36.4% vs 33.9%). After the toddler dose, tenderness was significantly higher among PCV7 subjects than PCV13 subjects (54.4% vs 48.8%; P=0.005). Frequencies of fever (≥38°C) were similar in both groups and mostly mild (≤39°C); incidence of moderate fever (>39°C to ≤40°C) with PCV13 was ≤2.8% after any infant dose and 5.0% after the toddler dose, compared with ≤2.6% and 7.3%, respectively, with PCV7. Fever >40°C was uncommon in both groups. Frequencies of decreased appetite, irritability, and sleep disturbances were similar in both groups. AEs were the types of conditions and symptoms expected in infants and children, and clinically significant differences between vaccine groups were not observed. PCV13 has a favorable safety profile similar to that of PCV7, a vaccine for which there is >10 years clinical experience. Copyright © 2013
Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines. Areas covered: This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared. Expert commentary: The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.
Full Text Available Respiratory tract infections are prevalent among Hajj pilgrims with pneumonia being a leading cause of hospitalization. Streptococcus pneumoniae is a common pathogen isolated from patients with pneumonia and respiratory tract infections during Hajj. There is a significant burden of pneumococcal disease in India, which can be prevented. Guidelines for preventive measures and adult immunization have been published in India, but the implementation of the guidelines is low. Data from Bangladesh are available about significant mortality due to respiratory infections; however, literature regarding guidelines for adult immunization is limited. There is a need for extensive awareness programs across India and Bangladesh. Hence, there was a general consensus about the necessity for a rapid and urgent implementation of measures to prevent respiratory infections in pilgrims traveling to Hajj. About ten countries have developed recommendations for pneumococcal vaccination in Hajj pilgrims: France, the USA, Kuwait, Qatar, Bahrain, the UAE (Dubai Health Authority, Singapore, Malaysia, Egypt, and Indonesia. At any given point whether it is Hajj or Umrah, more than a million people are present in the holy places of Mecca and Madina. Therefore, the preventive measures taken for Hajj apply for Umrah as well. This document puts forward the consensus recommendations by a group of twenty doctors following a closed-door discussion based on the scientific evidence available for India and Bangladesh regarding the prevention of respiratory tract infections in Hajj pilgrims.
[Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile].
Fernández V, José Pablo; Goecke H, Carola; von Borries, Cecilia; Tapia R, Natalia; Santolaya de P, María Elena
Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Spencer, Brady L; Shenoy, Anukul T; Orihuela, Carlos J; Nahm, Moon H
As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), carries the putative O-acetyltransferase gene wciZ The coding sequence of wciZ contains eight consecutive TA repeats [(TA) 8 ]. Replication slippage is thought to result in the addition or loss of TA repeats, subsequently causing frameshift and truncation of WciZ to yield a nonacetylated serotype, 15C. Using sensitive serological tools, we show that serotype 15C isolates whose wciZ contains seven or nine TA repeats retain partial O-acetylation, while serotype 15C isolates whose wciZ contains six TA repeats have barely detectable O-acetylation. We confirmed by inhibition enzyme-linked immunosorbent assay that (TA) 7 serotype 15C is ∼0.1% as acetylated as serotype 15B, while serotype 15X is nonacetylated. To eliminate the impact of genetic background, we created isogenic serotype 15B, (TA) 7 serotype 15C, and 15BΔ wciZ (15X) strains and found that reduction or absence of WciZ-mediated O-acetylation did not affect capsular shielding from phagocytes, biofilm formation, adhesion to nasopharyngeal cells, desiccation tolerance, or murine colonization. Sera from PPV23-immunized persons opsonized serotype 15B significantly but only slightly better than serotypes 15C and 15X; thus, PPV23 may not result in expansion of serotype 15C. Copyright © 2017 American Society for Microbiology.
Full Text Available Hypothesis: Blood group antibodies are natural antibodies that develop early in life in response to cross-reactive environmental antigens in the absence of antigen encounter. Even later in life structural similarities in saccharide composition between environmental antigens such as bacterial polysaccharides and blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype and affinity maturation of blood group anti-A/B antibodies. We adressed the question whether immunization with pneumococcal polysaccharide (PnP vaccine (PPV Pneumovax®23 could have such an effect in patients with with type I diabetes mellitus (DM I, an autoimmune disease where an aberrant immune response to microbial antigens likely plays a role.Methods: Anti-PnP IgM and IgG responses were determined by ELISA and the Diamed-ID Micro Typing System was used to screen anti-A/B antibody titer before and after Pneumovax®23 immunization in 28 healthy individuals and 16 patients with DM I. In addition, surface plasmon resonance (SPR technology using the Biacore® device and a synthetic blood group A/B trisaccharide as the antigen was applied to investigate IgM and IgG anti-A/B antibodies and to measure antibody binding dynamics. Results: All healthy individuals and DM I patients responded with anti-PnP IgM and IgG antibody production four to six weeks after Pneumovax®23 (Pn23 immunization, while no increase in blood group anti-A/B antibody titer was observed when measured by the Diamed-ID Micro Typing System. Interestingly, isotype-specific testing by SPR-technology revealed an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization in both patients and controls. No change in binding characteristics of blood group anti-A/B antibodies could be detected following Pn23 vaccination, supporting the assumption of an increase in IgG antibody titer with no or very little affinity maturation.Conclusion: The study provides evidence for epitope sharing
Manuel Alexander Haasis
Full Text Available The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies.A cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs in Philippine peso (Php per QALY gained (1 USD = 44.20 Php. Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty.With universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13 due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program.The inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers.
Farmaki, Paraskevi F; Chini, Maria C; Mangafas, Nikolaos M; Tzanoudaki, Marianna T; Piperi, Christina P; Lazanas, Marios Z; Spoulou, Vana S
Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/μL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/μL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. NCT03041051.
Incidence of invasive pneumococcal disease in 5-15 year old children with and without comorbidities in Germany after the introduction of PCV13: Implications for vaccinating children with comorbidities.
Weinberger, Raphael; Falkenhorst, Gerhard; Bogdan, Christian; van der Linden, Mark; Imöhl, Matthias; von Kries, Rüdiger
To describe the burden of suffering from IPD in children aged 5-15 years with and without comorbidities up to 5 years after the introduction of PCV13 in Germany and to identify the potential benefit for PCV13 and PPV23 vaccination. The surveillance of IPD for children children from 2010 to 2014 in Germany. Incidence was estimated by capture-recapture analysis with stratification by absence/presence of comorbidities. Coverage of the observed serotypes by different vaccines was assessed. 142 (Capture recapture-corrected: 437) cases were reported: 72.5% were healthy children and 27.5% had a comorbidity. The incidence of IPD related to children with comorbidities was 0.2 per 100,000. One third of these cases had serotypes not included in either vaccine. The remaining cases might benefit from pneumococcal vaccination but one third of all cases was not vaccinated. The additional potential benefit of PPV23 compared to PCV13 with respect to coverage was 10%. The incidence of IPD in children with comorbidities in Germany is low. Pneumococcal vaccination uptake in children with comorbidities should be increased, although only about two-thirds of the cases might be preventable by presently available vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.
Boccalini, Sara; Azzari, Chiara; Resti, Massimo; Valleriani, Claudia; Cortimiglia, Martina; Tiscione, Emilia; Bechini, Angela; Bonanni, Paolo
A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who had already completed their vaccination with PCV7, with the aim of extending the serotype coverage, triggered an animated scientific debate. The purpose of this study was to perform a clinical/economic evaluation of the administration of a dose of PCV13, in a catch-up programme, for children under 5 years of age, who had already received 3 doses of PCV7. A mathematical model of the clinical/economic impact of the adoption of 4 catch-up strategies with PCV13 (children up to 24, 36, 48 and 60 months old) was set up, with a vaccination coverage of 80%, versus immunization with 3 doses of PCV7 without the catch-up programme. The time span covered by the simulation was 5.5 years. The following clinical outcomes of infection were evaluated: hospitalised meningitis/sepsis, hospitalised bacteraemic pneumonias (complicated and uncomplicated), hospitalised non-bacteraemic pneumonias, and non-hospitalised pneumonias. The administration of one dose of PCV13 to children up to 60 months of age significantly reduces the number of cases of pneumococcal diseases (especially, non-hospitalised pneumonias, 80% of all events prevented, and hospitalised cases of non-bacteraemic pneumococcal pneumonias, 15% of all events prevented) and, subsequently, the relative cost for medical treatment. This results in savings for medical costs amounting to more than 1,000,000 Euros when vaccinating children under 24 months of age (up to almost 3 million Euros for children up to 60 months). More than half of those savings are attributable to avoided hospitalised cases of non-bacteraemic pneumococcal
Ingels, Helene; Rasmussen, Jeppe; Andersen, Peter Henrik
rate ratio 1.18; 95% CI [1.12-1.24]) with predominance of the serotypes 1.7F and 19A. CONCLUSIONS: We report a marked decline in incidence in IPD in both vaccinated and non-vaccinated age groups and a minor but statistically significant increase in incidence of IPD due to NVTs in both vaccinated...
Full Text Available Abstract Introduction We present a case of Streptococcus pneumoniae polyarticular septic arthritis in a patient with rheumatoid arthritis receiving a single infusion of infliximab. Case presentation A 38-year-old Japanese man with a 5-year history of seronegative rheumatoid arthritis had previously received sulphasalazine and methotrexate therapies and was on regular low-dose prednisolone therapy. Despite these treatments, his disease activity remained high and infliximab was introduced in addition to methotrexate, prednisolone, and folic acid. However, he was admitted to hospital with a fever of 40.6°C, chills, and polyarthralgia eight days after the first infusion of infliximab. His joints were swollen, painful, and warm. Laboratory data showed marked acute inflammation. He was diagnosed with bacterial septic polyarthritis, and emergency surgical joint lavage and drainage was performed at the knees along with needle aspiration and lavage of the ankles and right wrist. He was then given intravenous antibiotic therapy for 31 days. He made a good recovery and was discharged on day 37. Conclusions We believe this is the first reported case of severe pneumococcal septic arthritis requiring hospitalization in a patient treated with infliximab. S. pneumonia is now a well-recognized but uncommon cause of polyarticular septic arthritis that can lead to cessation of therapy, as in our patient's case.
Full Text Available Modern data of effectiveness prophylaxis of pneumococcal infection in children younger 1 year old with vaccine is presented in this article. Including of 7 - valency pneumococcal conjugated vaccine (PCV-7 in immunization program of some countries resulted in decrease of morbidity as in vaccinated group, as in all population. It was marked that vaccination with PCV-7 plays important pathogenetic role in termination of hidden forms of disease and prevention of spreading of pneumococcal infection, including the most severe types, hardly treated with antibiotics.Key words: children, pneumococcal infection, vaccination.
Le, Cheng-Foh; Jefferies, Johanna M; Yusof, Mohd Yasim Mohd; Sekaran, Shamala Devi; Clarke, Stuart C
In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.
Simon P Jochems
Full Text Available Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current vaccines targeting the polysaccharide capsule effectively prevent colonization, conferring herd protection within vaccinated communities. However, these vaccines cover only a subset of all circulating pneumococcal strains, and serotype replacement has been observed. Given the success of pneumococcal conjugate vaccine (PCV in preventing colonization in unvaccinated adults within vaccinated communities, reducing nasopharyngeal colonization has become an outcome of interest for novel vaccines. Here, we discuss the immunological mechanisms that control nasopharyngeal colonization, with an emphasis on findings from human studies. Increased understanding of these immunological mechanisms is required to identify correlates of protection against colonization that will facilitate the early testing and design of novel vaccines.
The global burden of pneumococcal diseases is high, with young children and adults≥50 years of age at highest risk of infection. Two types of vaccine are available for the prevention of pneumococcal diseases caused by specific Streptococcus pneumoniae serotypes: the pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccine (PCV7, PCV10, and PCV13). Despite pneumococcal immunization programs in adults and children, the burden in adults has remained high. Most European countries have national or local/regional vaccination recommendations. The objective of this review was to provide an overview of the government recommendations for pneumococcal vaccination outside routine childhood vaccination programs for 16 Western European countries as of August 2014. We found that recommendations for pneumococcal immunization across Europe are complex and vary greatly among countries in terms of age groups and risk groups recommended for vaccination, as well as which vaccine should be administered. Clarifying or simplifying these recommendations and improving their dissemination could help to increase pneumococcal vaccine uptake and decrease the high burden of pneumococcal diseases in adults, both through a direct effect of the vaccine and via a herd effect in unvaccinated individuals.
Ayala-Montiel, Octavio; Mascareñas de los Santos, César; García-Hernández, Delfino; Rendón-Muñiz, Jorge; García-Olvera, Laura
Pneumonia is the principal cause of morbidity and mortality in PEMEX medical services. Vaccination against influenza is 72% effective in preventing hospitalizations and 87% effective in preventing deaths related to this virus, and vaccination against pneumococcus is 60% effective in preventing invasive diseases by this microorganism. ACIP recommends use of both vaccines simultaneously in adults over 65 years of age. To describe the frequency, duration and severity of local and systemic reactions related to the simultaneous administration of vaccines against influenza and pneumococcus in adults over 55 years of age, and compare with reactions related to influenza vaccine. Two hundred-thirty two adults over 55 years of age were randomly assigned to two groups, group A (114 subjects) received influenza vaccine, group B (118 subjects) received influenza and pneumococcus vaccines simultaneously. Comparing the number of subjects with local reactions on the right arm between groups A and B (17 subjects vs. 27 subjects), differences were not statistically significative (p = 0.121). Systemic reactions were not statistically significative either (p = 0.126) when results were compared between both groups (30 from group A vs. 42 for group B). Simultaneous administration of influenza and pneumococcus vaccines has proven to be safety. In the absence of contraindications, there is no reason for not offering both vaccines in the same medical visit.
Gustavo Giachetto Larraz
Full Text Available OBJETIVO: Evaluar la relación costo-efectividad del programa de vacunación universal con la vacuna antineumocócica conjugada heptavalente (VCN7 en niños menores de 5 años en Uruguay. MÉTODOS: Se desarrolló un modelo Markov simulando una cohorte de 48 000 niños nacidos en 2007 y su evolución hasta los 76 años de edad. El caso base usó un esquema de tres dosis con una duración estimada de protección de cinco años. La presunción de eficacia y efectividad de la vacuna se realizó acorde con estudios realizados en Estados Unidos con ajuste a la prevalencia-incidencia de serotipos en Uruguay. Los resultados se expresaron como costo incremental por año de vida ganado (AVG y por año de vida [ganado] ajustado por calidad (AVAC. RESULTADOS: Para el caso base, el costo incremental fue de US$ 7 334,6 por AVG y US$ 4 655,8 por AVAC, previniéndose 8 muertes y 4 882 casos de otitis, 56 bacteriemias-sepsis, 429 neumonías y 7 meningitis. El modelo muestra sensibilidad a variaciones en eficacia, costo de la vacuna y tasa de mortalidad por neumonía. CONCLUSIONES: El programa de vacunación universal con VCN7 en Uruguay es altamente costo-efectivo y, en consecuencia, recomendable para otros países con carga de enfermedad neumocócica y cobertura de serotipos similares a Uruguay.OBJECTIVE: Evaluate the cost-effectiveness ratio of the program for universal vaccination with heptavalent pneumococcal conjugate vaccine (PCV7 in children under 5 years of age in Uruguay. METHODS: A Markov model was developed that simulated a cohort of 48 000 children born in 2007 and their progress to age 76. The baseline case used a regimen of three doses with estimated protection for five years. The presumption of vaccine efficacy and effectiveness was based on studies conducted in the United States with adjustment for serotype prevalence-incidence in Uruguay. The results were expressed as the incremental cost per life year gained (LYG and quality-adjusted life year
Nagel, J.; Saxne, T.; Geborek, P.
in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus...
Navne, Johan Emdal; Koch, Anders; Slotved, Hans-Christian
. Overall carriage rate of S. pneumoniae remained unchanged from 2011 to 2013 (51% and 56%, p=0.13), but significant serotype shifts were observed among both vaccinated and unvaccinated children with marked reductions in carriage of vaccine-type pneumococci, counterbalanced by increasing carriage of non...
McCollum, Eric D.; Nambiar, Bejoy; Deula, Rashid; Zadutsa, Beatiwel; Bondo, Austin; King, Carina; Beard, James; Liyaya, Harry; Mankhambo, Limangeni; Lazzerini, Marzia; Makwenda, Charles; Masache, Gibson; Bar-Zeev, Naor; Kazembe, Peter N.; Mwansambo, Charles; Lufesi, Norman; Costello, Anthony; Armstrong, Ben
Background The pneumococcal conjugate vaccine’s (PCV) impact on childhood pneumonia during programmatic conditions in Africa is poorly understood. Following PCV13 introduction in Malawi in November 2011, we evaluated the case burden and rates of childhood pneumonia. Methods and Findings Between January 1, 2012-June 30, 2014 we conducted active pneumonia surveillance in children pneumonia per Malawi guidelines, defined as fast breathing only, chest indrawing +/- fast breathing, or, ≥1 clinical danger sign. Since pulse oximetry was not in the Malawi guidelines, oxygenation pneumonia, a distinct category from clinical pneumonia. We quantified the pneumonia case burden and rates in two ways. We compared the period immediately following vaccine introduction (early) to the period with >75% three-dose PCV13 coverage (post). We also used multivariable time-series regression, adjusting for autocorrelation and exploring seasonal variation and alternative model specifications in sensitivity analyses. The early versus post analysis showed an increase in cases and rates of total, fast breathing, and indrawing pneumonia and a decrease in danger sign and hypoxemic pneumonia, and pneumonia mortality. At 76% three-dose PCV13 coverage, versus 0%, the time-series model showed a non-significant increase in total cases (+47%, 95% CI: -13%, +149%, p = 0.154); fast breathing cases increased 135% (+39%, +297%, p = 0.001), however, hypoxemia fell 47% (-5%, -70%, p = 0.031) and hospital deaths decreased 36% (-1%, -58%, p = 0.047) in children pneumonia, including hypoxemia and death, have markedly decreased. PMID:28052071
Haro, Kaoru; Ogawa, Masato; Hoshina, Takayuki; Kojiro, Masumi; Kusuhara, Koichi
This study aimed to compare hospitalization of children for pneumonia between secondary and tertiary medical facilities, which hospitalize many children without and with underlying diseases, respectively, after the introduction of the pneumococcal conjugate vaccine (PCV). Our retrospective study included children admitted to the Department of Pediatrics at Kitakyushu General Hospital, a secondary medical facility, and the Hospital of the University of Occupational and Environment Health, Japan, a tertiary medical facility, from 2009 to 2013 for pneumonia. We compared the change in the rate of hospitalization for pneumonia after the introduction of the 7-valent PCV between the secondary and tertiary medical facilities. Hospitalization of patients with pneumonia declined by 28.8% in our secondary medical facility. In particular, hospitalization for pneumonia other than confirmed mycoplasmal or viral pneumonia was significantly reduced by 49.2%. In contrast, hospitalization of patients with pneumonia did not decline in our tertiary medical facility. After the introduction of PCV, hospitalization of children for pneumonia was not reduced at the tertiary medical facility. Various other pathogens besides pneumococcus may be associated with the development of pneumonia in children with underlying diseases.
Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza
To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.
The present invention provides one or more immunogenic polypeptides for use in a preventive or therapeutic vaccine against latent or active infection in a human or animal caused by a Mycobacterium species, e.g. Mycobacterium avium subsp. paratuberculosis. Furthermore a single or multi-phase vaccine...... comprising the one or more immunogenic polypeptides is provided for administration for the prevention or treatment of infection with a Mycobacterium species, e.g. Mycobacterium avium subsp. paratuberculosis. Additionally, nucleic acid vaccines, capable of in vivo expression of the multi-phase vaccine...
Domínguez-Alegría, A R; Pintado, V; Barbolla, I
Invasive pneumococcal disease is a severe infection that mainly affects patients with associated comorbidity. The paediatric conjugate vaccination has resulted in a change in the adult vaccination strategy. The antibiotic resistance of pneumococcus is not currently a severe problem. Nevertheless, the World Health Organisation has included pneumococcus among the bacteria whose treatment requires the introduction of new drugs, such as ceftaroline and ceftobiprole. Although the scientific evidence is still limited, the combination of beta-lactams and macrolides is recommended as empiric therapy for bacteraemic pneumococcal pneumonia. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Full Text Available OBJECTIVE: To compare the costs and benefits of pneumococcal conjugate vaccination compared with no vaccination from the perspectives of the health care system and society. METHODS: Using data from established sources, we estimated the incidence and mortality due to invasive pneumococcal disease, pneumonia, and acute otitis media (AOM for a hypothetical birth cohort of children from birth to 5 years. RESULTS: A universal pneumococcal conjugate vaccination program was estimated capable of annually avoiding 1 047 cases of invasive disease, 58 226 cases of pneumonia, and 209 862 cases of AOM. When herd immunity effects were considered, the program prevented 1.3 million cases of pneumococcal disease and over 7 000 pneumococcal deaths. At a vaccination cost of R$ 51.12 (US$ 26.35 per dose, vaccination would cost annually R$ 4 289 (US$ 2,211 per disability-adjusted life years averted. This does not take into account herd immunity effects. CONCLUSIONS: At the current vaccine price, conjugate vaccination could be a cost-effective investment compared to other options to control childhood diseases. Further analysis is required to determine whether vaccination at the current price is affordable to Brazil.OBJETIVO: Comparar los costos y los beneficios de la aplicación de la vacuna conjugada antineumocócica en comparación con la no vacunación, desde las perspectivas del sistema de salud y la sociedad. MÉTODOS: A partir de fuentes reconocidas, se estimaron la incidencia y la mortalidad por enfermedad neumocócica invasora, neumonía y otitis media aguda (OMA para una cohorte hipotética de niños desde su nacimiento hasta los 5 años. RESULTADOS: Se estimó que un programa de vacunación universal con una vacuna conjugada antineumocócica sería capaz de evitar anualmente 1 047 casos de la enfermedad invasora, 58 226 casos de neumonía y 209 862 casos de OMA. Si se considera el efecto de la inmunidad de grupo, el programa evitaría 1,3 millones de casos
Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial.
van den Bergh, Menno R; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H; Sanders, Elisabeth A M
Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered. We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster. Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups. Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated.
... Cause Disease , May 30, 2018 NIH Begins Testing Ebola Treatment in Early-Stage Trial , May 23, 2018 ... visit the MedlinePlus flu site . Credit: NIAID Colorized structure of a prototype for a universal flu vaccine. ...
... Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention... information materials for rotavirus vaccine. DATES: Written comments are invited and must be received on or... (chickenpox), pneumococcal conjugate, rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and...
Erik H. Mercado
Full Text Available Objetivos. Determinar la frecuencia y distribución de serotipos de S. pneumoniae en portadores nasofaríngeos sanos menores de dos años previa al uso universal de la vacuna conjugada antineumocócica en el Perú. Materiales y métodos. Entre los años 2007 y 2009 se tomaron muestras de hisopado nasofaríngeo a 2123 niños sanos entre 2 y 24 meses de edad en los consultorios de crecimiento y desarrollo o vacunación de hospitales y centros de salud de siete ciudades del Perú: costa (Lima, Piura; sierra (Cusco, Abancay, Arequipa y Huancayo y selva (Iquitos. Las cepas de neumococo fueron aisladas e identificadas en el laboratorio central del proyecto en Lima y serotipificadas por reacción de Quellung en el Laboratorio de Referencia de Neumococo del Centro de Control y Prevención de Enfermedades. Resultados. Se encontró 27,0% (573/2123 de portadores nasofaríngeos sanos de neumococo. En las 526 cepas analizadas se encontraron 42 serotipos; los más frecuentes fueron: 19F (18,1%, 6B (14,3%; 23F (8,9% y 14 (6,5%. Conclusiones. La distribución de serotipos vacunales en las cepas analizadas fue de 50,0% para los serotipos presentes en la vacuna conjugada heptavalente; 50,2% para los serotipos presentes en la vacuna decavalente y 57,2% para la vacuna 13-valente.Objectives. To determine the carriage rate and serotype distribution of Streptococcus pneumoniae in the nasopharynx of healthy children younger than 2 years prior to the universal use of the pneumococcal conjugate vaccines in Peru. Materials and methods. Between 2007 and 2009 we collected nasopharyngeal swab samples from 2,123 healthy children aged 2 to 24 months in the vaccination and healthy children consultation offices of pediatric hospitals and health centers in 7 cities in Peru: on the coast (Lima, Piura, highlands (Cusco, Abancay, Arequipa and Huancayo and amazon basin (Iquitos. The pneumococcal strains were isolated and identified at the central laboratory of the project in Lima
Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M
To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.
Lai, Zengzu; Schreiber, John R
Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.
... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: drowsiness or temporary loss of appetite ( ...
... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: Drowsiness or temporary loss of appetite ( ...
Full Text Available Pneumococcal infection is one of the most widespread reasons for the development of infections of the respiratory passages (otitis, sinusitis in children. At the same time, it may act as an etiological factor of severe urgent conditions, such as pneumococcal meningitis and pneumococcal pneumonia, especially in children under 2 years old. A reliable method for preventing this infection is specific immunological prophylaxis. The article covers in detail the issue of vaccination in Russia and in other countries. The necessity of vaccination of all infants is demonstrated, as well as the necessity of participation in resolving this issue not only of pediatricians but governmental institutions as well in order to enhance safety and efficiency of vaccination and include this vaccine into the national calendar.Key words: pneumococcal infection, forms, complications, vaccination, national vaccination calendar, risk groups, children.
Sparding, Nadja; Dayie, Nicholas Tete Kwaku Dzifa; Mills, Richael O.
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular polysaccharide and more than 90 different serotypes are currently known. In this project, three distinct groups of pneumococcal carriage isolates from Gh...... in Ghana in that many new clones were identified. This supports the importance of continued monitoring of pneumococcal carriage in Ghana and elsewhere when vaccines, e.g., PCV-13, have been introduced to monitor the possible future spread of antimicrobial resistant clones....
Full Text Available oday, India is home to 99 million elderly people. By 2050, the number of elderly in this country will have gone up to 300 million1. With an increase in life expectancy from 32 years at the time of independence to 67.14 years in 20121, 10% of the population finds itself labeled as ‘senior citizen’. Inevitably, age brings with it comorbidities, immune senescence and pneumococcal disease. Pneumonia, in deference to its considerable morbidity and mortality, was exalted by Sir William Osler to its dubious pedestal of “Captain of all these Men of Death”. Unsurprisingly, immune debility and in several regions of the planet increasing antibiotic resistance, have ensured that pneumococcal pneumonia continues to take a large toll of senior citizens. Death rates have hardly budged over the last three decades. In India, pneumonia accounts for 25-30% deaths in the elderly3, a fatality rate almost unrivalled by most other terminal diseases. Among 15 high-burden countries, India has the dubious distinction of ranking third from last in the Global Action Plan for Pneumonia and Diarrhea (GAPPD4. During the World Immunization Week 2015 (April 24th to 30th, the ‘Close the Immunization Gap’ campaign gains crucial importance. Immunization, long vaunted as one of the most successful and cost-effective health interventions there is, prevent 2 to 3 million deaths every year, and saves enor-mous hospitalization costs and prevents loss of productivity. The recently published CAPiTA study (Community Acquired Pneumonia Immunization Trial in Adults, evaluated the efficacy of a novel 13-valent conju-gate vaccine for Pneumococcal pneumonia a vac-cine proven for its efficacy in children for the first time in older adults over 85,000 of them. Childhood vaccination with ‘PCV-13’, of course, was instrumental in reducing nasopharyngeal carriage of Strep pneumonia and decreasing the prevalence of Pneumococcal disease in the community at large. Altogether, the idea
Dagna O. Constenla
Full Text Available OBJECTIVES: To evaluate the economic impact of vaccination with the pneumococcal 7-valent conjugate vaccine (PCV7 in Brazil, Chile, and Uruguay. METHODS: A decision analytic model was constructed to compare pneumococcal vaccination of children 0-5 years old with no vaccination in Brazil, Chile, and Uruguay. Costs and health outcomes were analyzed from the societal perspective. Vaccine, demographic, epidemiologic, and cost data were incorporated into this economic analysis. RESULTS: At the rate of diphtheria-tetanus-pertussis (DTP vaccine coverage and a vaccine price of US$ 53 per dose, PCV7 was projected to prevent 23 474 deaths per year in children under 5 years old in the three countries studied, thus averting 884 841 disability-adjusted life years (DALYs yearly. To vaccinate the entire birth cohort of the three countries, total vaccine costs would be US$ 613.9 million. At US$ 53 per dose, the cost per DALY averted from a societal perspective would range from US$ 664 (Brazil to US$ 2 019 (Chile. At a cost of US$ 10 per dose, vaccine cost is lower than the overall cost of illness averted (US$ 125 050 497 versus US$ 153 965 333, making it cost effective and cost-saving. CONCLUSIONS: The results of this study demonstrate that the incorporation of PCV7 vaccine at US$ 53 per dose confers health benefits at extra costs. It is unclear whether vaccination at the current price is affordable to these countries.OBJETIVOS: Evaluar el impacto económico de la aplicación de la vacuna antineumocócica conjugada heptavalente (PCV7 en Brasil, Chile y Uruguay. MÉTODOS: Se elaboró un modelo analítico de decisiones para comparar la vacunación antineumocócica de los niños de 0-5 años de edad con la no vacunación, en Brasil, Chile y Uruguay. Los costos y los desenlaces para la salud se analizaron desde el punto de vista de la sociedad. Al análisis económico se incorporaron los costos y los datos demográficos, epidemiológicos y de la vacuna. RESULTADOS
Pneumococcal disease and vaccination in the Americas: an agenda for accelerated vaccine introduction Enfermedad neumocócica y vacunación antineumocócica en las Américas: programa de acción para la introducción acelerada de una vacuna
Full Text Available This piece summarizes the presentations and discussions at a meeting on pneumococcal disease surveillance in the Americas that was held in Mexico City, Mexico, on 2 November 2004. This meeting was organized by the Pan American Health Organization (PAHO and the Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP of the Global Alliance for Vaccines and Immunization (GAVI. The meeting participants reviewed the status of pneumococcal disease surveillance in the Region of the Americas, estimates of the burden of pneumococcal disease, the distribution of Streptococcus pneumoniae serotypes that cause invasive disease, the status of pneumococcal vaccine introduction, health economic analyses, and financial issues related to vaccine introduction. The meeting participants also worked to identify the next steps for generating the critical information needed to help make decisions on pneumococcal vaccine introduction. Coordinated pneumococcal disease surveillance for the Region of the Americas dates back to the 1993 establishment by PAHO of the Regional System for Vaccines (RSV project for surveillance of bacterial meningitis and pneumonia, including pneumococcal disease. Surveillance data from the RSV indicate that the distribution of major serotypes in the Americas has been stable over time (but that antibiotic resistance is increasing, with serotype 14 being the leading serotype isolated in most countries participating in RSV. Based on local serotype data from six of the RSV countries (Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay, the 7-valent vaccine would cover 65% of serotypes, the 9-valent vaccine would cover 77%, and the 11-valent vaccine would cover 83%.Este trabajo resume las presentaciones y los debates que hubo en una reunión sobre la vigilancia de las enfermedades neumocócicas en las Américas, celebrada en la ciudad de México, México, el 2 de noviembre de 2004. La reunión la habían organizado la
Community-acquired lobar pneumonia in children in the era of universal 7-valent pneumococcal vaccination: a review of clinical presentations and antimicrobial treatment from a Canadian pediatric hospital
Full Text Available Abstract Background Community-acquired pneumonia (CAP is a common cause of pediatric admission to hospital. The objectives of this study were twofold: 1 to describe the clinical characteristics of CAP in children admitted to a tertiary care pediatric hospital in the pneumococcal vaccination era and, 2 to examine the antimicrobial selection in hospital and on discharge. Methods A retrospective review of healthy immunocompetent children admitted to a tertiary pediatric hospital from January 2007 to December 2008 with clinical features consistent with pneumonia and a radiographically-confirmed consolidation was performed. Clinical, microbiological and antimicrobial data were collected. Results One hundred and thirty-five hospitalized children with pneumonia were evaluated. Mean age at admission was 4.8 years (range 0–17 years. Two thirds of patients had been seen by a physician in the 24 hours prior to presentation; 56 (41.5% were on antimicrobials at admission. 52 (38.5% of patients developed an effusion, and 22/52 (42.3% had pleural fluid sampled. Of 117 children who had specimens (blood/pleural fluid cultured, 9 (7.7% had pathogens identified (7 Streptococcus pneumoniae, 1 Group A Streptococcus, and 1 Rhodococcus. 55% of patients received 2 or more antimicrobials in hospital. Cephalosporins were given to 130 patients (96.1% in hospital. Only 21/126 patients (16.7% were discharged on amoxicillin. The median length of stay was 3 days (IQR 2–4 for those without effusion and 9 (IQR 5–13 for those with effusion. No deaths were related to pneumonia. Conclusions This study provides comprehensive data on the clinical characteristics of hospitalized children with CAP in the pneumococcal 7-valent vaccine era. Empiric antimicrobial choice at our institution is variable, highlighting a need for heightened antimicrobial stewardship.
Ballegaard, Vibe C; Schejbel, Lone; Hoffmann, Steen
was found. Despite immunization against S. pneumoniae and measurement of what was interpreted as protective levels of serotype-specific IgG antibodies after vaccination, the patient suffered from a third episode of IPD. CONCLUSIONS: Individuals with predisposing medical conditions or a history of severe......BACKGROUND: The risk of life-threatening and invasive infections with encapsulated bacteria is increased in patients with hyposplenia or asplenia. We report a case of recurrent invasive pneumococcal meningitis in a woman with previous unknown hyposplenia. She was vaccinated after the first episode...... of meningitis and developed sufficient levels of pneumococcal antibodies. The pneumococcal strains isolated were serotype 7 F and 17 F. To our knowledge, there has been no previously reported case of recurrent invasive pneumococcal disease in a pneumococcal vaccinated adult with hyposplenia and apparently...
Full Text Available Objetivo: Análisis de coste-efectividad de la vacunación antineumocócica pediátrica en España. Métodos: Se utilizó un modelo determinístico poblacional en forma de árbol de decisión con un horizonte temporal de 1 año para estimar el impacto de la vacunación con Synflorix® o Prevenar13® sobre la población menor de 2 años en España, bajo la perspectiva del Sistema Nacional de Salud. Los datos epidemiológicos se obtuvieron del Conjunto Mínimo Básico de Datos al alta hospitalaria y de la literatura. Los datos sobre costes se obtuvieron de bases de datos nacionales de costes sanitarios. Los principales resultados en salud medidos fueron los casos evitados de enfermedad neumocócica invasora, otitis media aguda (OMA, miringotomías y hospitalizaciones por neumonía. Todos los costes se expresaron en euros de 2010. La efectividad se midió en años de vida ajustados por calidad (AVAC. Resultados: El potencial demostrado por Synflorix® para prevenir episodios de OMA causados por Haemophilus influenzae no tipificable podría traducirse en la prevención adicional de 41.513 episodios de OMA, 36.324 prescripciones de antibióticos y 382 miringotomías, y supondrían la ganancia de 143 AVAC frente a Prevenar13®. El coste total de la vacunación con Synflorix® resultaría unos 22 millones de euros menor. Conclusiones: La vacunación antineumocócica de la población menor de 2 años en España con Synflorix®, en comparación con la vacunación con Prevenar13®, podría resultar en un mayor número de AVAC, así como en una reducción sustancial del coste total, resultando una estrategia dominante en términos de coste-efectividad.Objective: To perform a cost-effectiveness analysis of pediatric pneumococcal vaccination in Spain. Methods: A deterministic population-based model in the form of a decision-tree with a 1-year time horizon was used to estimate the impact of vaccination with Synflorix® or Prevenar13® in children aged less
Shak, Joshua R; Vidal, Jorge E; Klugman, Keith P
Streptococcus pneumoniae (the pneumococcus) is a common commensal inhabitant of the nasopharynx and a frequent etiologic agent in serious diseases such as pneumonia, otitis media, bacteremia, and meningitis. Multiple pneumococcal strains can colonize the nasopharynx, which is also home to many other bacterial species. Intraspecies and interspecies interactions influence pneumococcal carriage in important ways. Co-colonization by two or more pneumococcal strains has implications for vaccine serotype replacement, carriage detection, and pneumonia diagnostics. Interactions between the pneumococcus and other bacterial species alter carriage prevalence, modulate virulence, and affect biofilm formation. By examining these interactions, this review highlights how the bacterial ecosystem of the nasopharynx changes the nature and course of pneumococcal carriage. Copyright © 2012 Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background Updated population-based data on the frequency and distribution of risk factors for pneumococcal disease is scarce. This study investigated the prevalence of distinct comorbidities and underlying risk conditions related to an increasing risk of pneumococcal disease among Catalonian middle-aged and older adults. Methods Cross-sectional population-based study including 2,033,465 individuals aged 50 years or older registered at 01/01/2015 in the Catalonian Health Institute (Catalonia, Spain. The clinical research database of the Information System for the Development of Research in Primary Care (SIDIAP database was used to identify high-risk (asplenia and/or immunocompromising conditions and other increased-risk conditions (chronic pulmonary, cardiac or liver disease, diabetes mellitus, alcoholism and/or smoking among study subjects. Results Globally, 980,310 (48.2% of the 2,033,465 study population had at least one risk condition of suffering pneumococcal disease (55.4% in men vs 42.0% in women, p < 0.001; 41.7% in people 50–64 years vs 54.7% in persons 65 years or older, p < 0.001. An amount of 176,600 individuals (8.7% had high-risk conditions (basically immunocompromising conditions. On the other hand, 803,710 persons (39.5% had one or more other risk conditions. In fact, 212,255 (10.4% had chronic pulmonary diseases, 248,377 (12.2% cardiac disease, 41,734 (2.1% liver disease, 341,535 (16.8% diabetes mellitus, 58,781 (2.9% alcoholism and 317,558 (15.6% were smokers. Conclusion In our setting, approximately 50 % of overall persons 50 years or older may be considered at-risk population for pneumococcal disease (almost 10 % have high-risk conditions and 40 % have other risk conditions.
Bacterial meningitis is a serious infectious disease, involving the membranes surrounding the brain and spinal cord, and the subarachnoid space. In the Netherlands most common causative agents are Streptococcus pneumoniae (72%) and Neisseria meningitidis (11%). The incidence of pneumococcal
Brownfield, Elisha; Marsden, Justin E; Iverson, Patty J; Zhao, Yumin; Mauldin, Patrick D; Moran, William P
Missed opportunities to vaccinate and refusal of vaccine by patients have hindered the achievement of national health care goals. The meaningful use of electronic medical records should improve vaccination rates, but few studies have examined the content of these records. In our vaccine intervention program using an electronic record with physician prompts, paper prompts, and nursing standing orders, we were unable to achieve national vaccine goals, due in large part to missing information and patient refusal. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.
Objective: To study the consequences of low coverage levels of a single dose of measles vaccine. Results: mean age observed in measles cases was 2 years and 8 months with a range from 3 months to 8 years. Maximum number of cases reported were <1 year of age (n=22,32%). Fifty percent of cases were seen among vaccinated children. Seventy-five percent (n=51) had history of contact with a measles case. Pneumonia was the commonest complication followed by acute gastroenteritis, encephalitis, febrile convulsions, oral ulcers, oral thrush, eye changes of vitamin-A deficiency and pulmonary tuberculosis (T.B.) in descending order of frequency. Fifty four cases were successfully treated for complications of measles and discharged. Nine cases left against medical advice. Five patients died all of them had encephalitis either alone (n=1) or in combination with pneumonia and acute gastroenteritis (n=4). Conclusion: There is a dire need to increase the immunization coverage to reduce the rate of vaccine failure and achieve effective control of measles.(author)
Full Text Available 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H 1 N 1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large...
Efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine against acute otitis media and nasopharyngeal carriage in Panamanian children – A randomized controlled trial
Sáez-Llorens, Xavier; Rowley, Stella; Wong, Digna; Rodríguez, Mirna; Calvo, Arlene; Troitiño, Marisol; Salas, Albino; Vega, Vielka; Castrejón, Maria Mercedes; Lommel, Patricia; Pascal, Thierry G.; Hausdorff, William P.; Borys, Dorota; Ruiz-Guiñazú, Javier; Ortega-Barría, Eduardo; Yarzabal, Juan Pablo; Schuerman, Lode
ABSTRACT We previously reported 10-valent pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) efficacy in a double-blind randomized trial (ClinicalTrials.gov: NCT00466947) against various diseases, including acute otitis media (AOM). Here, we provide further analyses. In the Panamanian subset, 7,359 children were randomized (1:1) to receive PHiD-CV or control vaccine at age 2/4/6 and 15–18 months. Of these, 2,000 had nasopharyngeal swabs collected. AOM cases were captured when parents sought medical attention for children with AOM symptoms; surveillance was enhanced approximately 2 y into the study through regular telephone calls or home visits by study personnel, who advised parents to visit the clinic if their child had AOM symptoms. Mean follow-up was 31.4 months. Clinical AOM (C-AOM) cases were assessed by physicians and confirmed by otorhinolaryngologists. Middle ear fluid samples, taken from children with C-AOM after specific informed consent, and nasopharyngeal samples were cultured for pathogen identification. For 7,359 children, 2,574 suspected AOM cases were assessed by a primary healthcare physician; 649 cases were C-AOM cases as per protocol definition. From the 503 MEF samples collected, 158 resulted in a positive culture. In the intent-to-treat cohort (7,214 children), PHiD-CV showed VE against first C-AOM (24.0% [95% CI: 8.7, 36.7]) and bacterial (B-AOM) episodes (48.0% [20.3, 66.1]) in children children younger than 24 months, and reduced vaccine-serotype NPC. PMID:28368738
Full Text Available Abstract Background Streptococcus pneumoniae is a major cause of human disease, especially in pre-school children and elderly people, as well as in special risk groups such as asplenic, antibody deficient patients, or presenting disruption of natural barriers. The occurrence of pneumococcal disease has increased with the onset of the HIV epidemic and the emergence of drug-resistance. Case presentation We report the case of an HIV-1-infected patient who experienced three episodes of recurrent pneumococcal meningitis over a 4-year period, despite chemoprophylaxis and capsular vaccination. Conclusions Efficacy of anti-pneumococcal chemoprophylaxis and vaccination in HIV-infected patients are discussed in the light of this particular case.
Neralla, Sridhar; Meyer, Keith C
risk factors for DRSP. A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of pneumonia and antibacterial administration. The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs. If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep drug concentrations above the minimal inhibitory concentration that is effective for DRSP. Treatment guidelines and recent studies suggest that combination therapy with a beta-lactam and macrolide may be associated with a better outcome in hospitalised patients, and overuse of fluoroquinolones as a single agent may promote quinolone resistance. The ketolides represent a new class of macrolide-like antibacterials that are highly effective in vitro against macrolide- and azalide-resistant pneumococci. Pneumococcal vaccination with the currently available polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive pneumococcal disease), but more effective vaccines, such as nonconjugate protein vaccines, need to be developed that provide broad protection against pneumococcal infection.
Johnson, Elizabeth A; Harwell, Todd S; Donahue, Peg M; Weisner, M'liss A; McInerney, Michael J; Holzman, Greg S; Helgerson, Steven D
Vaccine-preventable diseases among adults are major contributing causes of morbidity and mortality in the United States. However, adult immunizations continue to be underutilized in both urban and rural areas. To evaluate the effectiveness of a community-wide education campaign and mailed reminders promoting pneumococcal immunizations to rural Medicare beneficiaries. We implemented a community-wide education campaign, and mailed reminders were sent to Medicare beneficiaries in 1 media market in Montana to increase pneumococcal immunizations. In a second distinct media market, mailed reminders only were sent to beneficiaries. The proportion of respondents aged 65 years and older aware of pneumococcal immunizations increased significantly from baseline to follow-up among respondents both in the education-plus-reminder (63% to 78%, P = 0.04) and the reminder-only (64% to 74%, P = 0.05) markets. Overall from 1998 to 1999, there was a 3.7-percentage-point increase in pneumococcal immunization claims for Medicare beneficiaries in the education-plus-reminder market and a 1.5-percentage-point increase in the reminder-only market. Medicare beneficiaries sent reminders in the education-plus-reminder market compared to those in the reminder-only market were more likely to have a claim for pneumococcal immunization in 1999 (odds ratio 1.18, 95% confidence interval 1.08 to 1.28). The results suggest that these quality improvement strategies (community education plus reminders and reminders alone) modestly increased pneumococcal immunization awareness and pneumococcal immunization among rural adults. Mailed reminder exposure was associated with an increased prevalence of pneumococcal immunizations between 1998 and 1999 and was augmented somewhat by the education campaign.
Contreras, Carmen Lucía; Verani, Jennifer R.; Lopez, María Renee; Paredes, Antonio; Bernart, Chris; Moscoso, Fabiola; Roldan, Aleida; Arvelo, Wences; Lindblade, Kim A.; McCracken, John P.
Background Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described. Methods Data from 2008–2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI). Results Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18–24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%. Conclusions An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala. PMID:26488871
Contreras, Carmen Lucía; Verani, Jennifer R; Lopez, María Renee; Paredes, Antonio; Bernart, Chris; Moscoso, Fabiola; Roldan, Aleida; Arvelo, Wences; Lindblade, Kim A; McCracken, John P
Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described. Data from 2008-2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI). Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18-24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%. An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala.
van Rijn, Piet A; Daus, Franz J; Maris-Veldhuis, Mieke A; Feenstra, Femke; van Gennip, René G P
Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV) transmitted by biting midges of the Culicoides genus. Outbreaks have been controlled successfully by vaccination, however, currently available BT vaccines have several shortcomings. Recently, we have developed BT Disabled Infectious Single Animal (DISA) vaccines based on live-attenuated BTV without expression of dispensable non-structural NS3/NS3a protein. DISA vaccines are non-pathogenic replicating vaccines, do not cause viremia, enable DIVA and are highly protective. NS3/NS3a protein is involved in virus release, cytopathogenic effect and suppression of Interferon-I induction, suggesting that the vaccination route can be of importance. A standardized dose of DISA vaccine for serotype 8 has successfully been tested by subcutaneous vaccination. We show that 10 and 100times dilutions of this previously tested dose did not reduce the VP7 humoral response. Further, the vaccination route of DISA vaccine strongly determined the induction of VP7 directed antibodies (Abs). Intravenous vaccination induced high and prolonged humoral response but is not practical in field situations. VP7 seroconversion was stronger by intramuscular vaccination than by subcutaneous vaccination. For both vaccination routes and for two different DISA vaccine backbones, IgM Abs were rapidly induced but declined after 14days post vaccination (dpv), whereas the IgG response was slower. Interestingly, intramuscular vaccination resulted in an initial peak followed by a decline up to 21dpv and then increased again. This second increase is a steady and continuous increase of IgG Abs. These results indicate that intramuscular vaccination is the optimal route. The protective dose of DISA vaccine has not been determined yet, but it is expected to be significantly lower than of currently used BT vaccines. Therefore, in addition to the advantages of improved safety and DIVA compatibility, the novel DISA vaccines will be cost
Werno, Anja M; Murdoch, David R
The laboratory diagnosis of invasive pneumococcal disease (IPD) continues to rely on culture-based methods that have been used for many decades. The most significant recent developments have occurred with antigen detection assays, whereas the role of nucleic acid amplification tests has yet to be fully clarified. Despite developments in laboratory diagnostics, a microbiological diagnosis is still not made in most cases of IPD, particularly for pneumococcal pneumonia. The limitations of existing diagnostic tests impact the ability to obtain accurate IPD burden data and to assess the effectiveness of control measures, such as vaccination, in addition to the ability to diagnose IPD in individual patients. There is an urgent need for improved diagnostic tests for pneumococcal disease--especially tests that are suitable for use in underresourced countries.
Gian Vincenzo Zuccotti
Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research
Joseph, SK; Ramaswamy, K
The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and Protein or Protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-Protein) and 48% (BmHAT Protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. PMID:23735679
Joseph, S K; Ramaswamy, K
The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and protein or protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-protein) and 48% (BmHAT protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. Copyright © 2013 Elsevier Ltd. All rights reserved.
Sónia T Almeida
Full Text Available Among the over 90 serotypes of Streptococcus pneumoniae described, serotypes 1, 5, and 7F account for a significant proportion of invasive disease worldwide and are now covered by the most recent 10- and 13-valent pneumococcal conjugate vaccines (PCVs. The epidemiology of these serotypes in carriage remains poorly studied because they are rarely detected. We aimed to gain insights into the epidemiology and population structure of serotypes 1, 5 and 7F carried by children in Portugal before PCV10 and PCV13 became widely used. Isolates obtained in cross-sectional studies carried out over a 15-year period (1996-2010 were retrospectively pooled and characterized. Of 5,123 pneumococci obtained, 70 were associated with serotypes 1 (n = 21, 5 (n = 7, and 7F (n = 42. The highest prevalence detected was 3.3% for serotype 1 in 2006, 1% for serotype 5 in 2009, and 3.3% for serotype 7F in 2006; Serotype 1 was associated with PMEN international clones Sweden(1-28(ST306 and Sweden(1-40(ST304; serotype 5 was associated with Colombia(5-19(ST289; and serotype 7F was associated with Netherlands(7F-39(ST191. All these isolates were fully susceptible. Most carriers of serotypes 1 (86%, 5 (86%, and 7F (91% were older than two years but a significant association with older age was only observed for serotype 7F (p = 0.006. Evidence for cross-transmission was obtained. In conclusion, we were able to detect and characterize the rarely carried serotypes 1, 5, and 7F among healthy children in Portugal. These data will constitute an important baseline for upcoming surveillance studies aimed to establish the impact of novel PCVs targeting these serotypes in carriage.
Wieten, Rosanne W.; Jonker, Emile F. F.; van Leeuwen, Ester M. M.; Remmerswaal, Ester B. M.; ten Berge, Ineke J. M.; de Visser, Adriëtte W.; van Genderen, Perry J. J.; Goorhuis, Abraham; Visser, Leo G.; Grobusch, Martin P.; de Bree, Godelieve J.
Prompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as
O'Brien, Megan A; Prosser, Lisa A; Paradise, Jack L; Ray, G Thomas; Kulldorff, Martin; Kurs-Lasky, Marcia; Hinrichsen, Virginia L; Mehta, Jyotsna; Colborn, D Kathleen; Lieu, Tracy A
New vaccines that offer protection against otitis media caused by nontypeable Haemophilus influenzae and by Moraxella catarrhalis are under development. However, the potential health benefits and economic effects of such candidate vaccines have not been systematically assessed. We created a computerized model to compare the projected benefits and costs of (1) the currently available 7-valent pneumococcal conjugate vaccine, (2) a candidate pneumococcal-nontypeable H influenzae vaccine that has been tested in Europe, (3) a hypothetical pneumococcal-nontypeable H influenzae-Moraxella vaccine, and (4) no vaccination. The clinical probabilities of acute otitis media and of otitis media with effusion were generated from multivariate analyses of data from 2 large health maintenance organizations and from the Pittsburgh Child Development/Otitis Media Study cohort. Other probabilities, costs, and quality-of-life values were derived from published and unpublished sources. The base-case analysis assumed vaccine dose costs of $65 for the 7-valent pneumococcal conjugate vaccine, $100 for the pneumococcal-nontypeable H influenzae vaccine, and $125 for the pneumococcal-nontypeable H influenzae-Moraxella vaccine. With no vaccination, we projected that 13.7 million episodes of acute otitis media would occur annually in US children aged 0 to 4 years, at an annual cost of $3.8 billion. The 7-valent pneumococcal conjugate vaccine was projected to prevent 878,000 acute otitis media episodes, or 6.4% of those that would occur with no vaccination; the corresponding value for the pneumococcal-nontypeable H influenzae vaccine was 3.7 million (27%) and for the pneumococcal-nontypeable H influenzae-Moraxella vaccine was 4.2 million (31%). Using the base-case vaccine costs, pneumococcal-nontypeable H influenzae vaccine use would result in net savings compared with nontypeable 7-valent pneumococcal conjugate use. Conversely, pneumococcal-nontypeable H influenzae-Moraxella vaccine use would not
Full Text Available Pneumococci are spread everywhere and they are very often a component of the microflora of the upper respiratory tracts. The level of the pneumococcus carriage is correlated with age. Among children the highest frequency is observed at the age of 4,5 years (up to 90% of cases, among adults it is 5–10%. According to international and Russian data, pneumococcal infection causes up to 76% of all the aetiologically deciphered cases of community cacquired pneumonia among adults and up to 94% (aggravated cases among children. The most frequent clinical forms of pneumococcal infection among children are acute otitis media (over 30%, pneumonia and meningitis (about 5–20% of all purulent bacterial meningitis, among adults — meningitis and sepsis. In 1998, in Russia was registered the first and still the only vaccine for the prevention of pneumococcal infection — Pneumo 23 (Sanofi Pasteur. The vaccine consists of 23 antic gens of the most dangerous pneumococcus serotypes and is used for the prevention of all the forms of pneumococcal infection. The composition of Pneumo 23 corresponds to 85% of pneumococcus serotypes circulating across Europe and to 90% serotypes resistant to penicillin. According to Russian data Pneumo 23 consists of about 80% of pneumococcus serotypes isolated in healthy carriers and ill with acute respiratory diseases and of 92% of serotypes in those suffering from acute bronchitis and pneumonia. The results of the clinical studies allow us to recommend the use of the given vaccine in a complex therapy of children, suffering from latent TB infection, often recurrent episodes of bronchopulmonary pathologies, ENT diseases, bronchial asthma and other chronic diseases.Key words: therapy, pediatrics, pneumonia, bronchial asthma, chronic obstructive lungs disease, prevention, treatment, pneumococcal infection.
Full Text Available While pneumococcal conjugate vaccines have been implemented in most countries worldwide, use in Asia has lagged in part because of a lack of data on the amount of disease that is vaccine preventable in the region. We describe pneumococcal serotypes elicited from 111 episodes of invasive pneumococcal disease (IPD from 2005 to 2013 among children and adults in Pakistan. Seventy-three percent (n = 81 of 111 IPD episodes were cases of meningitis (n = 76 in children 0-15 years and n = 5 among adults. Serotypes were determined by target amplification of DNA extracted from pneumococcal isolates (n = 52 or CSF specimens (n = 59. Serogroup 18 was the most common serogroup causing meningitis in children <5 years, accounting for 21% of cases (n = 13. The 10-valent pneumococcal conjugate vaccine (PCV 10 or PCV10- related serotypes were found in 61% (n = 47 of childhood (age 0-15 years meningitis episodes. PCV-13 increased this coverage to 63% (one additional serotype 19A; n = 48. Our data indicate that use of PCVs would prevent a large proportion of serious pneumococcal disease.
Roffe, T.J.; Jones, L.C.; Coffin, K.; Drew, M.L.; Sweeney, Steven J.; Hagius, S.D.; Elzer, P.H.; Davis, D.
Brucellosis has been eradicated from cattle in the states of Wyoming, Montana, and Idaho, USA. However, free-ranging elk (Cervus elaphus) that use feedgrounds in the Greater Yellowstone Area (GYA) and bison (Bison bison) in Yellowstone and Grand Teton national parks still have high seroprevalence to the disease and have caused loss of brucellosis-free status in Wyoming. Management tools to control or eliminate the disease are limited; however, wildlife vaccination is among the methods currently used by wildlife managers in Wyoming. We conducted a controlled challenge study of single calfhood vaccination. Elk calves, caught in January and February of 1999 and 2000 and acclimated to captivity for 3 weeks, were randomly assigned to control or vaccinate groups. The vaccinate groups received Brucetta abortus vaccine strain 19 (S19) by hand-delivered intramuscular injection. Calves were raised to adulthood and bred at either 2.5 or 3.5 years of age for 2000 and 1999 captures, respectively. Eighty-nine (44 controls, 45 vaccinates) pregnant elk entered the challenge portion of the study. We challenged elk at mid-gestation with pathogenic B. abortus strain 2308 by intraconjunctival instillation. Abortion occurred in significantly more (P = 0.002) controls (42; 93%) than vaccinates (32; 71%), and vaccine protected 25% of the vaccinate group. We used Brucella culture of fetus/calf tissues to determine the efficacy of vaccination for preventing infection, and we found that the number of infected fetuses/calves did not differ between controls and vaccinates (P = 0.14). Based on these data, single calfhood vaccination with S19 has low efficacy, will likely have only little to moderate effect on Brucella prevalence in elk, and is unlikely to eradicate the disease in wildlife of the GYA.
Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing
This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%– vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage. PMID:25760670
Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing
This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.
Mills, Nikki; Best, Emma J; Murdoch, David; Souter, Melanie; Neeff, Michel; Anderson, Trevor; Salkeld, Lesley; Ahmad, Zahoor; Mahadevan, Murali; Barber, Colin; Brown, Colin; Walker, Cameron; Walls, Tony
This study aims to describe the microbiology of middle ear fluid (MEF) in a cohort of children vaccinated with Streptococcus pneumoniae conjugate vaccine (PCV7) having ventilation tube insertion. Nasopharyngeal (NP) carriage of otopathogens in these children is compared with children without history of otitis media. Between May and November 2011, MEF and NP samples from 325 children aged otitis-prone comparison group of 137 children had NP samples taken. A questionnaire was completed by both groups. Immunisation coverage with at least one dose of PCV7 was 97%. Haemophilus influenzae was cultured in 19.4% of MEF and was polymerase chain reaction (PCR) positive in 43.4%. S. pneumoniae and Moraxella catarrhalis were cultured in otitis prone group. S. pneumoniae was more commonly found in the nasopharynx of children with ear disease (41% vs. 29%). 19F was the most prominent S. pneumoniae serotype in NP samples of both groups, but no serotype dominated in MEF. Ninety-five per cent of H. influenzae isolates were confirmed to be non-typeable H. influenzae. In this cohort of children with established ear disease requiring surgical intervention, non-typeable H. influenzae is the dominant pathogen in both the nasopharynx and MEF. © 2014 The Authors. Journal of Paediatrics and Child Health published by Wiley Publishing Asia Pty Ltd on behalf of Paediatrics and Child Health Division. (The Royal Australasian College of Physicians).
Simons, Malorie; Scott-Sheldon, Lori A J; Risech-Neyman, Yesenia; Moss, Steven F; Ludvigsson, Jonas F; Green, Peter H R
Celiac disease has been associated with hyposplenism, and multiple case reports link celiac disease and pneumococcal infections; however, increased risk of pneumococcal infection in celiac disease has not been confirmed. The purpose of this study was to conduct a systematic review to determine the risk of pneumococcal infections in celiac disease. Relevant studies were identified using electronic bibliographic searches of PubMed, OVID, Medline, and EMBASE (1980 to February 2017) and reviewing abstracts from major conferences in gastroenterology. Using number of events in celiac patients and referent patients, we calculated a summary relative risk of pneumococcal infections. All analyses were conducted in Comprehensive Meta-Analysis software using random-effects assumptions. Of a total of 156 articles, 3, representing 3 large databases (the Swedish National Inpatient Register; the Oxford Record Linkage Study; and the English National Hospital Episode Statistics) were included. Each compared patients with celiac disease and confirmed pneumococcal infection to a specific reference group: inpatients and/or the general population. Overall, the odds of pneumococcal infection were higher among hospitalized celiac patients compared with controls (odds ratio 1.66; 95% confidence interval 1.43-1.92). There was no evidence of heterogeneity (Q = 1.17, P = .56, I 2 = 0%). Celiac disease is associated with an increased risk of pneumococcal infection. Preventive pneumococcal vaccination should be considered for those with celiac disease, with special attention to those aged 15-64 years who have not received the scheduled pneumococcal vaccination series as a child. Copyright © 2018 Elsevier Inc. All rights reserved.
Gladstone, R A; Jefferies, J M; Faust, S N; Clarke, S C
Streptococcus pneumoniae is an important pathogen worldwide. Accurate sampling of S. pneumoniae carriage is central to surveillance studies before and following conjugate vaccination programmes to combat pneumococcal disease. Any bias introduced during sampling will affect downstream recovery and typing. Many variables exist for the method of collection and initial processing, which can make inter-laboratory or international comparisons of data complex. In February 2003, a World Health Organisation working group published a standard method for the detection of pneumococcal carriage for vaccine trials to reduce or eliminate variability. We sought to describe the variables associated with the sampling of S. pneumoniae from collection to storage in the context of the methods recommended by the WHO and those used in pneumococcal carriage studies since its publication. A search of published literature in the online PubMed database was performed on the 1st June 2012, to identify published studies that collected pneumococcal carriage isolates, conducted after the publication of the WHO standard method. After undertaking a systematic analysis of the literature, we show that a number of differences in pneumococcal sampling protocol continue to exist between studies since the WHO publication. The majority of studies sample from the nasopharynx, but the choice of swab and swab transport media is more variable between studies. At present there is insufficient experimental data that supports the optimal sensitivity of any standard method. This may have contributed to incomplete adoption of the primary stages of the WHO detection protocol, alongside pragmatic or logistical issues associated with study design. Consequently studies may not provide a true estimate of pneumococcal carriage. Optimal sampling of carriage could lead to improvements in downstream analysis and the evaluation of pneumococcal vaccine impact and extrapolation to pneumococcal disease control therefore
... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine • Mild Problems: Drowsiness or temporary loss of appetite ( ...
Vasconcelos, Pedro Fc
The yellow fever (YF) vaccine has been used since the 1930s to prevent YF, which is a severe infectious disease caused by the yellow fever virus (YFV), and mainly transmitted by Culicidae mosquitoes from the genera Aedes and Haemagogus . Until 2013, the World Health Organization (WHO) recommended the administration of a vaccine dose every ten years. A new recommendation of a single vaccine dose to confer life-long protection against YFV infection has since been established. Recent evidence published elsewhere suggests that at least a second dose is needed to fully protect against YF disease. Here, we discuss the feasibility of administering multiple doses, the necessity for a new and modern vaccine, and recommend that the WHO conveys a meeting to discuss YFV vaccination strategies for people living in or travelling to endemic areas.
Madeddu, Giordano; Fois, Alessandro Giuseppe; Pirina, Pietro; Mura, Maria Stella
In this review, we focus on the clinical features, diagnosis and management of pneumococcal pneumonia in HIV-infected and noninfected patients, with particular attention to the most recent advances in this area. Classical clinical features are found in young adults, whereas atypical forms occur in immunocompromised patients including HIV-infected individuals. Bacteremic pneumococcal pneumonia is more frequently observed in HIV-infected and also in low-risk patients, according to the Pneumonia Severity Index (PSI). Pneumococcal pneumonia diagnostic process includes physical examination, radiologic findings and microbiologic diagnosis. However, etiologic diagnosis using traditional culture methods is difficult to obtain. In this setting, urinary antigen test, which recognizes Streptococcus pneumoniae cell wall C-polysaccharide, increases the probability of etiologic diagnosis. A correct management approach is crucial in reducing pneumococcal pneumonia mortality. The use of the PSI helps clinicians in deciding between inpatient and outpatient management in immunocompetent individuals, according to Infectious Diseases Society of America (IDSA)-American Thoracic Society (ATS) guidelines. Recent findings support PSI utility also in HIV-infected patients. Recently, efficacy of pneumococcal vaccine in reducing pneumococcal disease incidence has been evidenced in both HIV-infected and noninfected individuals. Rapid diagnosis and correct management together with implementation of preventive measures are crucial in order to reduce pneumococcal pneumonia related incidence and mortality in HIV-infected and noninfected patients.
Full Text Available Prevalence of pneumococcal serotypes in carriage and disease has been described but absolute serotype colonisation densities have not been reported. 515 paediatric nasal swab DNA extracts were subjected to lytA qPCR and molecular serotyping by microarray. Absolute serotype densities were derived from total pneumococcal density (qPCR cycle threshold and standard curve and relative abundance (microarray and varied widely. Compared to all serotype densities observed, the strongest evidence of differences was seen for serotypes 21 and 35B (higher and 3, 38 and non-typeables (lower (p<0.05 with a similar hierarchy when only a single serotype carriage was assessed. There was no evidence of any overall density differences between children with single or multiple serotypes detected but serotypes with mid-range densities were more prevalent. The hierarchy of distinct pneumococcal serotype carriage densities described here for the first time, may help explain the dynamics of transmission between children.
Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.
Yun, Ki Wook; Choi, Eun Hwa; Lee, Hoan Jong
Pneumococcal surface protein A (PspA) is an important virulence factor of pneumococci and has been investigated as a primary component of a capsular serotype-independent pneumococcal vaccine. Thus, we sought to determine the genetic diversity of PspA to explore its potential as a vaccine candidate. Among the 190 invasive pneumococcal isolates collected from Korean children between 1991 and 2016, two (1.1%) isolates were found to have no pspA by multiple polymerase chain reactions. The full length pspA genes from 185 pneumococcal isolates were sequenced. The length of pspA varied, ranging from 1,719 to 2,301 base pairs with 55.7-100% nucleotide identity. Based on the sequences of the clade-defining regions, 68.7% and 49.7% were in PspA family 2 and clade 3/family 2, respectively. PspA clade types were correlated with genotypes using multilocus sequence typing and divided into several subclades based on diversity analysis of the N-terminal α-helical regions, which showed nucleotide sequence identities of 45.7-100% and amino acid sequence identities of 23.1-100%. Putative antigenicity plots were also diverse among individual clades and subclades. The differences in antigenicity patterns were concentrated within the N-terminal 120 amino acids. In conclusion, the N-terminal α-helical domain, which is known to be the major immunogenic portion of PspA, is genetically variable and should be further evaluated for antigenic differences and cross-reactivity between various PspA types from pneumococcal isolates.
Yoon Hong Choi
Full Text Available England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7 with its 13-valent equivalent (PCV13, partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether.A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13.Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000-62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether.Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch.
Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong
Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.
Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis Rentabilidad médica de la vacunación antineumocócica en América Latina y el Caribe: un análisis regional
Full Text Available OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.OBJETIVO: En América Latina y el Caribe, la vacunación sistemática de niños contra Streptococcus pneumoniae podría requerir inversiones considerables de los gobiernos y organizaciones donantes. Al evaluar estas inversiones se requiere
Comparison of 2 commercial single-dose Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines on pigs dually infected with M. hyopneumoniae and PRRSV.
Park, Changhoon; Kang, Ikjae; Seo, Hwi Won; Jeong, Jiwoon; Choi, Kyuhyung; Chae, Chanhee
The objective of this study was to compare the efficacy of 2 different commercial Mycoplasma hyopneumoniae vaccines and porcine reproductive and respiratory syndrome virus (PRRSV) vaccines in regard to growth performance, microbiological and immunological analyses, and pathological observation from wean to finish (175 d of age). Pigs were administered M. hyopneumoniae and PRRSV vaccines at 7 and 21 d of age, respectively, or both at 21 d old and then challenged with both M. hyopneumoniae and PRRSV at 49 d old. Significant (P hyopneumoniae, M. hyopneumoniae-specific interferon-γ secreting cells, and macroscopic and microscopic lung lesions. Induction of interleukin-10 following PRRSV vaccination does not interfere with the immune responses induced by M. hyopneumoniae vaccine. The present study demonstrated that the single-dose vaccination regimen for M. hyopneumoniae and PRRSV vaccine is efficacious for controlling coinfection with M. hyopneumoniae and PRRSV based on clinical, microbiological, immunological, and pathological evaluation.
Comparison of two-dose priming plus 9-month booster with a standard three-dose priming schedule for a ten-valent pneumococcal conjugate vaccine in Nepalese infants: a randomised, controlled, open-label, non-inferiority trial.
Hamaluba, Mainga; Kandasamy, Rama; Upreti, Shyam R; Subedi, Giri R; Shrestha, Shrijana; Bhattarai, Shiva; Gurung, Meeru; Pradhan, Rahul; Voysey, Merryn; Gurung, Santosh; Pradhan, Shachi; Thapa, Anushil K; Maharjan, Rakesh; Kiran, Usha; Kerridge, Simon A; Hinds, Jason; van der Klis, Fiona; Snape, Matthew D; Murdoch, David R; Kelly, Sarah; Kelly, Dominic F; Adhikari, Neelam; Thorson, Stephen; Pollard, Andrew J
Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond. Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood. We did an open-label, randomised, parallel group, controlled trial in healthy infants aged 40-60 days from Kathmandu, Nepal. Participants were randomly allocated (4:4:5 ratio) to receive PCV10 in addition to routine immunisations either as a two-dose prime and boost (2+1), three-dose prime (3+0), or two doses after completion of the initial study phase (0+2). We used a computer generated randomisation list with randomly varying block sizes. We followed up participants at age 2-4 years together with a group of unvaccinated controls. Sera were analysed for opsonophagocytic activity, protein D, and PCV10 serotype-specific IgG. Laboratory staff was masked to intervention group assignment. The primary outcome measure was to determine the proportion of participants in the 2+1 group at age 10 months with specific IgG for serotypes 1, 5, and 14 of at least 0·2 μg/mL in the per-protocol population. The secondary outcomes were non-inferiority (within 10% levels) at age 18 weeks for the proportion of participants in the 2+1 group compared with the 3+0 group with serotypes 1, 5, and 14 specific IgG of at least 0·2 μg/mL; the proportion of participants with PCV10 serotype-specific IgG of at least 0·2 μg/mL and opsonophagocytic activity reciprocal titre of at least 8 at ages 18 weeks and 10 months; and nasopharyngeal pneumococcal serotype-specific carriage rates at age 9 months in each study
Kirkham, Lea-Ann S; Wiertsema, Selma P; Corscadden, Karli J; Mateus, Tulia; Mullaney, Gemma L; Zhang, Guicheng; Richmond, Peter C; Thornton, Ruth B
The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group ( P otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children. Copyright © 2017 Kirkham et al.
De Graeve, Diana; Beutels, Philippe
In this review, the economic aspects of pneumococcal pneumonia are analysed, including the costs, cost effectiveness and cost benefit of treatment and prevention. We identified eight cost-of-illness studies, 15 analyses comparing the costs of different treatment options and 15 economic evaluations of prevention that met our search criteria. The studies were conducted largely in Europe and the US. Most pertained to community-acquired pneumonia (CAP) in general, without specific analysis of pneumococcus-related illness. Many of the studies were considered to be of poor quality for the following reasons: comparison without randomisation or control variables, disregard of health outcomes, small sample size, restriction of costs to drug costs and vague or disputable sources of cost information. In the US, hospitalisation costs resulting from CAP can be estimated to be between US 7,000 dollars and US 8,000 dollars per admission or US 4 million dollars per 100,000 population. Hospitalisation costs are significant (representing about 90% of total costs), but are much lower in Europe than in the US (one-third to one-ninth of the US estimates in the UK and Spain, respectively). In general, economic studies of treatment for pneumococcal pneumonia are in line with clinical evidence. A drug with proven clinical effectiveness would also appear to be supported from an economic stand point. Furthermore, economic data support an early switch from an intravenous to an oral antibacterial, the use of quinolones for inpatients with CAP, and also the use of guidelines built on clinical evidence. Of all the possible preventive strategies for pneumococcal pneumonia, only vaccination has been subjected to economic evaluation. Pneumococcal polysaccharide vaccine seems relatively cost effective (and potentially cost saving) for those between 65 and 75 years of age, for military recruits and for HIV positive patients with a sufficiently high CD4 cell count. Evaluations of the pneumococcal
Zhang, Xiaoshu; An, Jing; Tu, Aixia; Liang, Xuefeng; Cui, Fuqiang; Zheng, Hui; Tang, Yu; Liu, Jianfeng; Wang, Xuxia; Zhang, Ningjing; Li, Hui
ABSTRACT Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine. PMID:27494260
S. G. Gubanova
Full Text Available The article describes the results of studying the effectiveness of vaccination of children with allergic disorders and frequently ill children against pneumococcal diseases. The effectiveness and good tolerability of the vaccine was detected. A follow-up study of the vaccinated children was performed. The positive effect of vaccination on the incidence of acute respiratory diseases, acute adenoiditis and acute otitis media in all groups of children was shown. The positive effect of vaccination on the degree of hyperplasia of adenoid tissue in the nasopharynx of frequently ill children was proved.
Ba, I D; Ba, A; Faye, P M; Thiongane, A; Attiyé Kane, M; Sonko, A; Diop, A; Deme Ly, I; Diouf, F N; Ndiaye, O; Leye, M M M; Cissé, M F; Ba, M
We aimed to describe the clinical, epidemiological, and outcome characteristics of IPD case patients hospitalized at the Albert-Royer National Children's Hospital (French acronym CHNEAR) to evaluate the disease burden of IPDs in a pediatric hospital of Dakar (Senegal). All children aged 0-15 years hospitalized at the CHNEAR between January 1st, 2008 and December 31st, 2013 for a documented IPD were included in the study. Medical history, risk factors, clinical, bacteriological, and outcome data was collected. Data was then analyzed using the SPSS software, version 16 (Pearson's Chi(2) test: a P-valueSenegal. Infants<2 years of age are particularly affected. The very high case fatality (17%) was significantly associated with meningeal infection sites hence the need for better access to pneumococcal vaccines. Copyright © 2015. Published by Elsevier SAS.
Ingels, Helene; Lambertsen, Lotte; Harboe, Zitta B
%, and 78% of the cases would have been covered by the 7-, 10-, and 13-valent pneumococcal conjugate vaccines, respectively. Conclusions: Of children with an IPD episode, 2.4% experienced rIPD, and an underlying disease was documented in 66% of these children. Investigation of underlying conditions...... laboratory-confirmed cases of IPD in children aged 0-15 y were identified from the Neisseria and Streptococcus Reference Laboratory, Statens Serum Institut, Denmark for the period 1980-2013. rIPD was defined as isolation of Streptococcus pneumoniae from any normally sterile site ≥ 30 days after an initial...... positive culture. Clinical data were obtained for all children with rIPD. Results: Of all children with IPD, 2.4% (59/2418) experienced at least 1 episode of rIPD, and an underlying condition was documented in 39 (66%). Immune deficiency due to transplantation (n = 9) was the most common disease; however...
Full Text Available Abstract Background The first meningococcal serogroup C (MenC conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed.
Park, Nina J; Sklaroff, Laura Myerchin; Gross-Schulman, Sandra; Hoang, Khathy; Tran, Helen; Campa, David; Scheib, Geoffrey; Guterman, Jeffrey J
Streptococcus pneumoniae is a principal cause of serious illness, including bacteremia, meningitis, and pneumonia, worldwide. Pneumococcal immunization is proven to reduce morbidity and mortality in high-risk adult and elderly populations. Current pneumococcal vaccination practices are suboptimal in part because of recommendation complexity, the high cost of provider-driven immunization interventions, and outreach methods that are not patient-centric. These barriers are amplified within the safety net. This paper identifies efforts by the Los Angeles County Department of Health Services to increase pneumococcal immunization rates for adult indigent patient populations. A 4-part approach will be used to increase vaccination rates: (1) protocol driven care, (2) staff education, (3) electronic identification of eligible patients, and (4) automated patient outreach and scheduling. The proposed analytics plan and potential for scalability are described. (Population Health Management 2016;19:240-247).
... Prevention, Immunization Action Coalition) - PDF Also in Spanish Topic Image MedlinePlus Email Updates Get Pneumococcal Infections updates ... ray Meningitis - pneumococcal Sputum gram stain Related Health Topics Meningitis Pneumonia Sepsis Sinusitis Streptococcal Infections National Institutes ...
Wei, Benjamin P C; Shepherd, Robert K; Robins-Browne, Roy M; Clark, Graeme M; O'Leary, Stephen J
Both clinical data and laboratory studies demonstrated the risk of pneumococcal meningitis post-cochlear implantation. This review examines strategies to prevent post-implant meningitis. Medline/PubMed database; English articles after 1980. Search terms: cochlear implants, pneumococcus meningitis, streptococcus pneumonia, immunization, prevention. Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted. The presence of inner ear trauma as a result of surgical technique or cochlear implant electrode array design was associated with a higher risk of post-implant meningitis. Laboratory data demonstrated the effectiveness of pneumococcal vaccination in preventing meningitis induced via the hematogenous route of infection. Fibrous sealing around the electrode array at the cochleostomy site, and the use of antibiotic-coated electrode array reduced the risk of meningitis induced via an otogenic route. The recent scientific data support the U.S. Food and Drug Administration recommendation of pneumococcal vaccination for the prevention of meningitis in implant recipients. Nontraumatic cochlear implant design, surgical technique, and an adequate fibrous seal around the cochleostomy site further reduce the risk of meningitis. Copyright © 2010 American Academy of Otolaryngology–Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.
Eichmann, Klaus; Krause, Richard M
During the first decade of the twentieth century, the German bacteriologist Fred Neufeld, later Director of the Robert Koch-Institute in Berlin, first described the differentiation of pneumococci into serotypes on the basis of type-specific antisera. This finding was essential for subsequent research at the Rockefeller Institute of Medical Research (RIMR) in New York, and elsewhere, aiming for the conquest of human pneumococcal pneumonia, including antiserum therapy, the discovery that the type-specific antigens were carbohydrates, and the development of effective multivalent pneumococcal polysaccharide vaccines. Moreover, on the basis of pneumococcal serotypes Fred Griffith, in 1928 in London, discovered pneumococcal transformation, and Oswald T. Avery and coworkers, in 1944 at RIMR, identified DNA as the transforming substance. This sequence of events, leading to today's knowledge that genes consist of DNA, was initiated by a farsighted move of Simon Flexner, first Director of the RIMR, who asked Neufeld to send his pneumococcal typing strains, thus setting the stage for pneumococcal research at RIMR. Here, we describe Fred Neufeld's contributions in this development, which have remained largely unknown.
Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines Distribución de serotipos de neumococos aislados de pacientes pediátricos con otitis media aguda e infecciones invasivas y su cobertura potencial a través de vacunas conjugadas
Full Text Available A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AÜM and invasive infections (INV. Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326 were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.Se realizó un estudio prospectivo descriptivo sobre la distribución de serotipos de neumococos aislados de niños con otitis media aguda (OMA y con infecciones invasivas (INV en un período de 16 meses. Se incluyeron 89 niños con INV neumocócicas y 324 con un primer episodio de OMA. Trescientos cuarenta y seis patógenos se aislaron de las secreciones de oído medio obtenidas de 250 pacientes. Se identificaron 30 serotipos y los más prevalentes fueron el 14, 19A, 9V, 3, 19F, 6A, 23F y 18C en OMA y el 14, 1, 19A, 5, 12F, 6B y 18C en INV. La cobertura potencial con la vacuna PCV10 sería de 46,5 % y 60,7 % para neumococos involucrados en OMA y en INV, respectivamente; con la PCV13, esta sería de 71,7 % y 73 %. La PCV10 conjugada con una proteína de Haemophilus tendría una cobertura inmunológica del 39,9 % para OMA, contra una cobertura del 18,5 % de la PCV13. Sin embargo, las diferencias en la prevención de INV fueron determinantes a la hora de considerar
Jansen, Angelique G S C; Hak, Eelko; Veenhoven, Reinier H; Damoiseaux, Roger A M J; Schilder, Anne G M; Sanders, Elisabeth A M
BACKGROUND: Acute otitis media (AOM) is a very common early infancy and childhood disease. The marginal benefits of antibiotics on AOM, the increasing problem of bacterial resistance to antibiotics, and the huge estimated direct and indirect annual costs associated with otitis media (OM) have
Fortanier, Alexandre C.; Venekamp, Roderick P.; Boonacker, Chantal W. B.; Hak, Eelko; Schilder, Anne G. M.; Sanders, Elisabeth A. M.; Damoiseaux, Roger A. M. J.
BACKGROUND: Acute otitis media (AOM) is a very common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual
Reisman, Jonathan; Rudolph, Karen; Bruden, Dana; Hurlburt, Debby; Bruce, Michael G; Hennessy, Thomas
Alaska Native children have high invasive pneumococcal disease (IPD) rates, and lack of in-home running water has been shown to have a significant association with infection. Pneumococcal conjugate vaccines reduced IPD; however, this population saw substantial replacement disease and colonization with nonvaccine serotypes. We evaluated risk factors for nasopharyngeal pneumococcal colonization in Alaska Native adults and children. We conducted annual surveys from 2008 through 2011 of residents of all ages in 8 rural Alaskan villages. Interviews were conducted, medical charts were reviewed, and nasopharyngeal swabs were cultured for Streptococcus pneumoniae. Multivariate logistic regression models were developed for 3 age groups (under 10 years, 10-17 years, and 18 years and older) to determine risk factors for colonization. We obtained 12 535 nasopharyngeal swabs from 4980 participants. Our population lived in severely crowded conditions, and 48% of households lacked in-home running water. In children water, household crowding, and more children in the home. Pneumococcal vaccination status was not associated with colonization. In older children and adults, increased number of persons in the household was associated with pneumococcal colonization. Higher colonization prevalence may partially explain increased IPD rates seen in those lacking in-home water services. Improving availability of sanitation services and reducing household crowding may reduce the burden of IPD in this population. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Jaeger, Veronika K.; Hoffman, Hal M.; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N.; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A.
Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS
Full Text Available Abstract Background Pneumococcal polysaccharide vaccination rates among adults 65 years and older or less than 65 years with high risk medical conditions are still below Healthy People 2010 recommended levels of 90%. This study was designed to: 1 assess self-reported pneumococcal vaccination rates following health center level interventions to increase adult vaccination rates; and 2 determine factors associated with vaccination. Methods Tailored interventions to increase immunizations were implemented at two inner-city health centers. We surveyed 375 patients 50 years of age and older. Multivariate logistic regression examines the predictors of 1 self-reported pneumococcal vaccination and 2 combined self-reported influenza and pneumococcal vaccination. Both of these models were stratified by age group (50–64 years and 65 years and older. Results Pneumococcal vaccination rates were 45% by self-report, 55% by medical record review, 69% for patients 65 years old and older, 32% for patients 50–64 years; they did not differ by race. Receipt of the previous season's influenza vaccine was significantly related to pneumococcal vaccination among both younger and older patients. Receiving both the pneumococcal vaccine and the most recent influenza vaccine compared with receiving neither, among younger patients was related to unemployment, more frequent physician visits, and belief that those who do not receive the flu shot are more susceptible to the flu. For older patients, receipt of both vaccines was related to nonsmoking status, believing that friends/family think the patient should be vaccinated, seeing posters advertising flu shot clinics, and belief that those who do not receive the flu shot are more susceptible to the flu. Conclusion Our findings suggest that improving overall pneumococcal vaccination rates among eligible adults, has the potential to eliminate racial disparities. Interventions delivering vaccination messages specific to older
Full Text Available BACKGROUND: Identification of high-risk populations for serious infection due to S. pneumoniae will permit appropriately targeted prevention programs. METHODS: We conducted prospective, population-based surveillance for invasive pneumococcal disease and laboratory confirmed pneumococcal pneumonia in homeless adults in Toronto, a Canadian city with a total population of 2.5 M, from January 1, 2002 to December 31, 2006. RESULTS: We identified 69 cases of invasive pneumococcal disease and 27 cases of laboratory confirmed pneumococcal pneumonia in an estimated population of 5050 homeless adults. The incidence of invasive pneumococcal disease in homeless adults was 273 infections per 100,000 persons per year, compared to 9 per 100,000 persons per year in the general adult population. Homeless persons with invasive pneumococcal disease were younger than other adults (median age 46 years vs 67 years, P<.001, and more likely than other adults to be smokers (95% vs. 31%, P<.001, to abuse alcohol (62% vs 15%, P<.001, and to use intravenous drugs (42% vs 4%, P<.001. Relative to age matched controls, they were more likely to have underlying lung disease (12/69, 17% vs 17/272, 6%, P = .006, but not more likely to be HIV infected (17/69, 25% vs 58/282, 21%, P = .73. The proportion of patients with recurrent disease was five fold higher for homeless than other adults (7/58, 12% vs. 24/943, 2.5%, P<.001. In homeless adults, 28 (32% of pneumococcal isolates were of serotypes included in the 7-valent conjugate vaccine, 42 (48% of serotypes included in the 13-valent conjugate vaccine, and 72 (83% of serotypes included in the 23-valent polysaccharide vaccine. Although no outbreaks of disease were identified in shelters, there was evidence of clustering of serotypes suggestive of transmission of pathogenic strains within the homeless population. CONCLUSIONS: Homeless persons are at high risk of serious pneumococcal infection. Vaccination, physical structure changes
Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S
In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.
Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Ciglenecki, Iza; Luquero, Francisco J; Azman, Andrew S; Cabrol, Jean-Clement
Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.
Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E
No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral
Full Text Available No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50 caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50. Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1- Y. pestis.VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single
Moore, Matthew R; Whitney, Cynthia G
Two decades ago, the Emerging Infections Program of the US Centers for Disease Control and Prevention implemented what seemed like a simple yet novel idea: a population- and laboratory-based surveillance system designed to identify and characterize invasive bacterial infections, including those caused by Streptococcus pneumoniae. This system, known as Active Bacterial Core surveillance, has since served as a flexible platform for following trends in invasive pneumococcal disease and studying vaccination as the most effective method for prevention. We report the contributions of Active Bacterial Core surveillance to every pneumococcal vaccine policy decision in the United States during the past 20 years.
Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula
The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.
Bellver Capella, Vincente
Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.
Park, Su-Jin; Seo, Hwi Won; Park, Changhoon; Chae, Chanhee
The objective of this study was to determine the effects of Mycoplasma hyopneumoniae and/or porcine reproductive and respiratory syndrome virus (PRRSV) vaccination on dually infected pigs. In total, 72 pigs were randomly divided into nine groups (eight pigs per group), as follows: five vaccinated and challenged groups, three non-vaccinated and challenged groups, and a negative control group. Single-dose vaccination against M. hyopneumoniae alone decreased the levels of PRRSV viremia and PRRSV-induced pulmonary lesions, whereas single-dose vaccination against PRRSV alone did not decrease nasal shedding of M. hyopneumoniae and mycoplasma-induced pulmonary lesions in the dually infected pigs. The M. hyopneumoniae challenge impaired the protective cell-mediated immunity induced by the PRRSV vaccine, whereas the PRRSV challenge did not impair the protective cell-mediated immunity induced by the M. hyopneumoniae vaccine. The present study provides swine practitioners and producers with efficient vaccination regimes; vaccination against M. hyopneumoniae is the first step in protecting pigs against co-infection with M. hyopneumoniae and PRRSV. Copyright © 2014 Elsevier Ltd. All rights reserved.
Trzciński, Krzysztof; Li, Yuan; Weinberger, Daniel M; Thompson, Claudette M; Cordy, Derrick; Bessolo, Andrew; Malley, Richard; Lipsitch, Marc
Competitive interactions between Streptococcus pneumoniae strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and in vitro measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes in vivo that is driven mainly, but not exclusively, by the capsule itself. Streptococcus pneumoniae (pneumococcus) is the leading cause of death due to respiratory bacterial infections but also a commensal frequently carried in upper airways. Available vaccines induce immune responses against polysaccharides coating pneumococcal cells, but with over 90 different capsular types (serotypes) identified, they can only target strains of the selected few serotypes most prevalent in disease. Vaccines not only protect vaccinated individuals against disease but also protect by
Scott Pangonis MD
Full Text Available Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date.
Harboe, Zitta B; Thomsen, Reimar W; Riis, Anders
BACKGROUND: Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD). METHODS AND FINDINGS: In a nationwide population-based...
Rahmberg Andrew R
Full Text Available Abstract Background Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection. Results Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array. Conclusions Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent TH1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1.
Porter, R.D.; Guild, W.R.
The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 x 10 10 to 4 x 10 10 PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages ω3 and ω8 each have linear double-stranded DNA of 33 x 10 6 daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol percent, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs several-fold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, ω3 and ω8 have D 37 values of 33 and 55 J/m 2 , respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between ω3 and ω8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages
Conclusion: Pneumococcal resistance was significant in this group of children with easy access to paediatric services and antibiotic use. The implication of such high resistance for the treatment of pneumococcal diseases is that high-dose amoxicillin is the preferred empirical oral therapy for treatment of otitis media.
Full Text Available Rift Valley fever virus (RVFV (genus Phlebovirus, family Bunyaviridae is an arbovirus that causes severe disease in humans and livestock in sub-Saharan African countries. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, neuroinvasiveness and neurovirulence of MP-12 in mice may be a concern when vaccinating certain individuals, especially those that are immunocompromised. We have developed a novel, single-cycle replicable MP-12 (scMP-12, which carries an L RNA, M RNA mutant encoding a mutant envelope protein lacking an endoplasmic reticulum retrieval signal and defective for membrane fusion function, and S RNA encoding N protein and green fluorescent protein. The scMP-12 underwent efficient amplification, then formed plaques and retained the introduced mutation after serial passages in a cell line stably expressing viral envelope proteins. However, inoculation of the scMP-12 into naïve cells resulted in a single round of viral replication, and production of low levels of noninfectious virus-like particles. Intracranial inoculation of scMP-12 into suckling mice did not cause clinical signs or death, a finding which demonstrated that the scMP-12 lacked neurovirulence. Mice immunized with a single dose of scMP-12 produced neutralizing antibodies, whose titers were higher than in mice immunized with replicon particles carrying L RNA and S RNA encoding N protein and green fluorescent protein. Moreover, 90% of the scMP-12-immunized mice were protected from wild-type RVFV challenge by efficiently suppressing viremia and replication of the challenge virus in the liver and the spleen. These data demonstrated that scMP-12 is a safe and immunogenic RVFV vaccine candidate.
Roffe, Thomas J.; Jones, Lee C.; Coffin, Kenneth; Sweeney, Steven J.; Williams, Beth; Quist, Charlotte
Brucellosis in Greater Yellowstone Area (GYA) bison and elk has been a source of controversy and focus of the Greater Yellowstone Interagency Brucellosis Committee (GYIBC) for years. Brucellosis has been eradicated from cattle in the 3 states of Wyoming, Montana, and Idaho and all three states currently are classified as “brucellosis free” with regard to livestock. Yet free-ranging elk that attend feedgrounds in the GYA, and bison in Yellowstone and Grand Teton National Parks, still have high seroprevalence to the disease and are viewed as a threat to the state-federal cooperative national brucellosis eradication program. Recently, cattle in eastern Idaho were found infected with brucellosis and transmission was apparently from fed elk. The GYIBC, formed of state and federal agencies involved in wildlife and livestock management in the 3 states, has committed to eventual elimination of the disease from wildlife. Management tools to control or eliminate the disease are limited; however, wildlife vaccination is one of the methods currently employed. Effective wildlife vaccination depends on dose efficacy, deliverability, and safety to non-targeted species. We commenced a single-dose efficacy study of vaccine Brucella abortus strain 19 (S19) in elk in 1999.
Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.
Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589
Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.
Avaliação da resposta humoral à vacina pneumocócica 7-valente em crianças com Aids Evaluación de la vacuna neumocócica 7-valente en la respuesta humoral de niños con SIDA Evaluation of humoral response to heptavalent pneumococcal conjugate vaccine in HIV-infected children
Isabel de Camargo Costa
Paulo (Sureste de Brasil, en 2002-2003. La dosis de anticuerpos IgG contra los polisacáridos de la cápsula neumocócica fue realizada por medio de ensayo inmuno enzimático (ELISA. Los anticuerpos fueron dosificados inmediatamente antes y un mes después de la aplicación de la segunda dosis de la vacuna. Se utilizaron dos criterios para evaluar la respuesta a la vacuna: títulos de anticuerpos ? 1,3 ?g/mL en la serología post-inmunización y aumento ?4 veces en los títulos de la serología post-inmunización con relación a la pre-inmunización. RESULTADOS: Para el primer criterio (?1,3 ?g/mL, 26 (65% niños obtuvieron respuesta serológica con la vacuna, 12 (30% de ellas presentaron títulos de IgG post-inmunización en niveles de por lo menos 1,3 ?g/mL para todos los serotipos. Para el segundo criterio (incremento >4 veces en los títulos para cuatro serotipos o mas, se obtuvo respuesta serológica en 15 (37,5% niños. CONCLUSIONES: La respuesta frente a la vacuna fue considerada satisfactoria, con aumento estadísticamente significativo de los títulos geométricos promedios post-vacunales con relación a los pre-vacunales para todos los serotipos estudiados.OBJECTIVE: Invasive pneumococcal disease is a major cause of death in HIV-infected children. The objective of the study was to assess the quantitative antibody response to the seven pneumococcal serotypes of heptavalent pneumococcal conjugate vaccine in a group of HIV-infected children. METHODS: Study comprising 40 HIV-infected children aged between 2 and 9 years followed up in a specialized outpatient clinic in São Paulo, Brazil, between 2002 and 2003. Enzyme immunoassay (ELISA was used to measure IgG antibody titers against pneumococcus capsule. Antibodies were measured immediately before and 1 month after the second dose of the vaccine. Two response criteria were used: IgG titers >1.3 µg/mL in the post-immunization serology and an increase of at least 4-fold in post- compared to pre
Vintiñi, Elisa O; Medina, Marcela S
At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB) with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei), when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA) for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV) and heat-killed (LcM) was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed. Nasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I). These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M) induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and LcM were found. Live and heat-killed L
Vintiñi Elisa O
Full Text Available Abstract Background At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei, when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV and heat-killed (LcM was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed. Results Nasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I. These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and
Sankaranarayanan, Rengaswamy; Joshi, Smita; Muwonge, Richard; Esmy, Pulikottil Okkuru; Basu, Partha; Prabhu, Priya; Bhatla, Neerja; Nene, Bhagwan M; Shaw, Janmesh; Poli, Usha Rani Reddy; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Tommasino, Massimo; Pawlita, Michael; Gheit, Tarik; Waterboer, Tim; Sehr, Peter; Pillai, Madhavan Radhakrishna
Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV
Falleiros-Arlant, Luiza Helena; Berezin, Eitan Naaman; Avila-Aguero, Maria Luisa; Pirez, Maria Catalina; Gentile, Angela; Richardson, Vesta; Brea, Jose; Mariño, Cristina
Some medical conditions constitute important risk factors for the development of invasive pneumococcal diseases in children and adolescents aged from 5 to 19 years. Conjugate vaccines have potential efficacy in this scenario, but are not available in many Latin American public healthcare systems for this age group. This study aimed to estimate the preventable fraction of invasive pneumococcal diseases among individuals aged from 5 to 19 years with associated risk factors for its development. Data regarding the Latin America population, risk factors prevalence and conjugate vaccines efficacy were obtained from the literature. Total population at risk ranged from 17.3 to 64.6 million of individuals and asthma was the most impacting risk factor. According to SIREVA, PCV13 provided a 62.9% serotypes coverage in individuals from 5 to 29 years in 2012, potentially increasing the covered population from [8,338,457-31,057,620] with PCV10 to [10,906,356-40,622,078] with PCV13. To date, according to available efficacy data, the hypothetically immunized population ranged from 11.4 to 42.4 million, representing 7.0% to 26.0% of the total population in this age group. Vaccination in risk groups should be encouraged, as it potentially contributes to the reduction in the number of cases of invasive pneumococcal disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Full Text Available Objectives: To investigate the molecular epidemiology of pneumococcal isolates in Chongqing, China. Methods: In this cross-sectional study, 51 invasive Streptococcus pneumoniae (S. pneumoniae strains were from children with invasive pneumococcal disease (IPD and 32 carriage strains from healthy children from January 2010 to December 2013 at the Children’s Hospital of Chongqing Medical University, Chongqing, China. Multilocus sequence typing was used to identify the sequence types (STs. Capsular serotypes were determined by multiplex polymerase chain reaction. Drug susceptibility and resistance was determined by minimum inhibitory concentrations. Results: In this study, 11 serotypes were identified among the 83 S. pneumoniae clinical isolates tested. Prevalent serotypes were 19A (20.4%, 6A/B (20.4%, 19F (15.7%, 14 (14.5%, and 23F (10.8%. Serotype 19F was the most frequent carriage strain, and serotype 19A was the most frequent invasive strain. The ST983 was the most prevalent ST for carriage strains, and ST320 was the most prevalent ST for invasive strains. For gene analysis, psaA (99.5% and piaA (98.6% were present and much conserved in all pneumococci tested. The cps2A and pcsB genes were more frequent in invasive isolates than carriage strains. Antimicrobial resistance rates of invasive pneumococcal isolates to erythromycin, penicillin, meropenem, cefotaxime, and clindamycin were higher than the carriage isolates from children. Conclusion: Our epidemiological evidence shows that 19A, 6A/B, 19F, 14, and 23F remain the most prevalent serotypes, which can be targeted by PCV13. Genotypes and drug resistance varied between carriage and invasive strains. The PsaA and PiaA may be good protein vaccine candidates.
Spijkerman, J.; van Gils, E.J.M.; Veenhoven, R.H.; Hak, E.; Yzerman, E.P.F.; van den Ende, A.; Wijmenga-Monsuur, A.J.; van den Dobbelsteen, G.P.J.M.; Sanders, E.A.M.
To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) program, we conducted a cross-sectional observational study on nasopharyngeal carriage of Streptococcus pneumoniae 3 years after implementation of the program in the Netherlands. We compared pneumococcal serotypes in
Wanderci Marys Oliveira Abrão
Full Text Available INTRODUCTION: In 2010, to reduce the occurrence of serious pneumococcal disease, the Ministry of Health in Brazil incorporated the 10-valent pneumococcal vaccine in the immunization schedule of children younger than two years of age. The objective of this study was to evaluate the impact of vaccination on the incidence of infectious respiratory diseases in infants before and after the introduction of the 10-valent pneumococcal vaccine. METHODS: This cross-sectional study involved primary care and hospital networks from a city in Minas Gerais State, Brazil, between 2009 and 2012. RESULTS: A 40% reduction in the prevalence of community-acquired pneumonia (CAP was observed after introducing the pneumococcal conjugate vaccine. Male children were 28% more likely to develop the disease. The prevalence ratio ([PR] = 1.96, 95% CI: 1.52 to 2.53, p < 0.05 suggested that not being vaccinated was associated with the occurrence of pneumonia. The prevalence of CAP was 70% lower (PR 0.30, 95% CI: 0.24 to 0.37, p<0.05 in children vaccinated as recommended compared to children with delayed vaccination, suggesting that the updated vaccine schedule improves protection. CONCLUSIONS: Immunization with the 10-valent pneumococcal vaccine appeared to reduce the number of pneumonia cases in children during the study period. Prospective studies are needed to confirm the efficacy of the vaccine against the occurrence of pneumococcal pneumonia.
Zimmerman, Richard K; Brown, Anthony E; Pavlik, Valory N; Moehling, Krissy K; Raviotta, Jonathan M; Lin, Chyongchiou J; Zhang, Song; Hawk, Mary; Kyle, Shakala; Patel, Suchita; Ahmed, Faruque; Nowalk, Mary Patricia
To test the effectiveness of a step-by step, evidence-based guide, the 4 Pillars Practice Transformation Program, to increase adult pneumococcal vaccination. Randomized controlled cluster trial (RCCT) in Year 1 (June 1, 2013 to May 31, 2014) and pre-post study in Year 2 (June 1, 2014 to January 31, 2015) with data analyzed in 2016. Baseline year was June 1, 2012, to May 31, 2013. Demographic and vaccination data were derived from deidentified electronic medical record extractions. Primary care practices (n = 25) stratified according to metropolitan area (Houston, Pittsburgh), location (rural, urban, suburban), and type (family medicine, internal medicine), randomized to receive the intervention in Year 1 (n = 13) or Year 2 (n = 12). Individuals aged 65 and older at baseline (N = 18,107; mean age 74.2; 60.7% female, 16.5% non-white, 15.7% Hispanic). The 4 Pillars Program, provider education, and one-on-one coaching of practice-based immunization champions. Outcome measures were 23-valent pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV) vaccination rates and percentage point (PP) changes in vaccination rates. In the Year 1 RCCT, PPSV vaccination rates increased significantly in all intervention and control groups, with average increases ranging from 6.5 to 8.7 PP (P < .001). The intervention was not related to greater likelihood of PPSV vaccination. In the Year 2 pre-post study, the likelihood of PPSV and PCV vaccination was significantly higher in the active intervention sites than the maintenance sites in Pittsburgh but not in Houston. In a RCCT, PPSV vaccination rates increased in the intervention and control groups in Year 1. In a pre-post study, private primary care practices actively participating in the 4 Pillars Practice Transformation Program improved PPSV and PCV uptake significantly more than practices that were in the maintenance phase of the study. © 2016, Copyright the Authors Journal compilation © 2016, The American
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals...
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...
Tran, T.H.; Nguyen, T.D.; Nguyen, T.T.; Ninh, T.T.V.; Tran, N.B.C.; Nguyen, V.M.H.; Tran, T.T.N.; Cao, T.T.; Pham, V.M.; Nguyen, T.C.B.; Tran, T.D.H.; Pham, V.T.; To, S.D.; Campbell, J.I.; Stockwell, E.; Schultsz, C.; Simmons, C.P.; Glover, C.; Lam, W.; Marques, F.; May, J.P.; Upton, A.; Budhram, R.; Dougan, G.; Farrar, J.; Nguyen, V.V.C.; Dolecek, C.
Background: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)
Tran, Tinh Hien; Nguyen, Thi Dung; Nguyen, Thanh Truong; Ninh, Thi Thanh Van; Tran, Nguyen Bich Chau; Nguyen, Van Minh Hoang; Tran, Thi Thu Nga; Cao, Thu Thuy; Pham, Van Minh; Nguyen, Thi Cam Binh; Tran, Thi Diem Ha; Pham, Van Toi; To, Song Diep; Campbell, James I.; Stockwell, Elaine; Schultsz, Constance; Simmons, Cameron P.; Glover, Clare; Lam, Winnie; Marques, Filipe; May, James P.; Upton, Anthony; Budhram, Ronald; Dougan, Gordon; Farrar, Jeremy; Nguyen, Van Vinh Chau; Dolecek, Christiane
The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with
Marsman FR; Akkermans AM; Hendriksen CFM; de Jong WH
This document presents the results of a validation study to the use of a single dilution assay in potency testing of the diphtheria component of DPT-polio vaccines. Based on historical data of multi-dilution assays on 27 consecutive batches a simulation study was performed to test the actual
Victor, J; Knudsen, J D; Nielsen, L P
A total of 162 anti-HAV-negative healthy adults were immunized with a single high dose (1440 ELISA units = 1 ml) of inactivated hepatitis A vaccine and a booster was given at month 6. Antibodies were measured after modification of a commercial ELISA kit, enabling quantification of titres down to 6...
Vermeij, Renee; Leffers, Ninke; Hoogeboom, Baukje-Nynke; Hamming, Ineke L. E.; Wolf, Rinze; Reyners, Anna K. L.; Molmans, Barbara H. W.; Hollema, Harry; Bart, Joost; Drijfhout, Jan W.; Oostendorp, Jaap; van der Zee, Ate G. J.; Melief, Cornelis J.; van der Burg, Sjoerd H.; Daemen, Toos; Nijman, Hans W.
The purpose of the current phase II single-arm clinical trial was to evaluate whether pretreatment with low-dose cyclophosphamide improves immunogenicity of a p53-synthetic long peptide (SLP) vaccine in patients with recurrent ovarian cancer. Patients with ovarian cancer with elevated serum levels
Ingels, Helene; Schejbel, Lone; Lundstedt, A C
examined. RESULTS: In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response......BACKGROUND: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory......-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency. METHODS: Cases of rIPD in children 0-15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer...
Cristina Aparecida Borges Laval
Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.
Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral
We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant
Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm
BACKGROUND: Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult
Full Text Available Introduction: Coeliac disease can be associated with hyposplenism and splenic atrophy, which may increase the patient’s risk for fatal infections caused by Streptococcus pneumoniae or Pneumococcus. It is general opinion that many more patients with coeliac disease have died from hyposplenism-related infections than those reported in literature. Case report: A 62-year-old woman with recently diagnosed coeliac disease was hospitalized with high fever, disorientation, and nuchal rigidity. Cerebral computed tomography was negative. Laboratory tests showed an elevated leukocyte count and very high levels of C reactive protein. The cerebrospinal fluid (CSF contained an increased number of mononuclear cells associated with a low glucose level and high protein concentrations. The CSF culture was positive for Streptococcus pneumoniae. Neurological conditions rapidly deteriorated with the onset of coma, and magnetic resonance imaging of the brain revealed initial signs of encephalitis extending above and below the tentorium. Abdominal ultrasonography disclosed splenic hypotrophy that raised the suspicion of hyposplenism. The diagnosis of hyposplenism was confirmed by demonstration of Howell-Jolly bodies in a peripheral blood smear. Discussion: This is the first reported case of pneumococcal meningoencephalitis caused by splenic hypofunction in a patient with coeliac disease. When coeliac disease is diagnosed with a marked delay in an elderly patient, spleen function should always be assessed. If impaired, the patient should undergo vaccination with pneumococcal conjugate vaccine to prevent pneumococcal infections.
Samir K Saha
Full Text Available BACKGROUND: Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. METHODS AND FINDINGS: Cases with suspected IPD had blood or cerebrospinal fluid (CSF collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%-26% of cases. Ninety eight percent (45/46 of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4-256.3. The serotype-2 strains had three closely related pulsed field gel electrophoresis types. CONCLUSIONS: S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2
[Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age].
Albrecht, Piotr; Antczak, Adam; Hryniewicz, Waleria; Skoczyńska, Anna; Radzikowski, Andrzej; Kedziora-Kornatowska, Kornelia; Bernatowska, Ewa; Stompór, Tomasz; Grodzicki, Tomasz; Gyrczuk, Ewa; Imiela, Jacek; Jedrzejczak, Wiesław; Windak, Adam
Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD
Aka Akt?rk, ?lk?; G?rek Dilekta?l?, Asl?; ?eng?l, Aysun; Musaffa Salep?i, Banu; Oktay, Nuray; D?ger, Mustafa; Ar?k Ta?y?kan, Hale; Durmu? Ko?ak, Nagihan
Background: Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. Aims: To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Study Design: Multi-centre cross-sectional study. Methods: Patients admi...
Vacinação contra influenza e pneumococo na insuficiência cardíaca: uma recomendação pouco aplicada Vacunación contra influenza y neumococo en la insuficiencia cardíaca: una recomendación poco aplicada Influenza and pneumococcal vaccination in heart failure: a little applied recommendation
Wolney de Andrade Martins
estudio observacional realizado en Teresópolis, región serrana fluminense, fueron utilizadas tres estrategias: (I estudio de las requisiciones para vacuna contra INF y/o PNM en la Secretaría Municipal de Salud, entre 2004 y 2006; (II averiguación directa a 61 pacientes con IC atendidos en la atención básica sobre su situación de vacuna contra INF y PNM; (III averiguación directa sobre situación de vacuna contra INF y PNM a 81 pacientes con IC crónica descompensada atendidos en la única emergencia abierta a la red pública. RESULTADOS: En la estrategia I, la vacunación contra INF y/o PNM fue de 15,3% de aquellos con indicaciones por enfermedades cardiovasculares y respiratorias. La mediana del tiempo entre la indicación y la vacunación fue de 32 días. En la estrategia II, el porcentual de vacunados contra INF, con edad > 60 años, fue de 23,1%, y de 24,6% contra PMN en todas las edades. En la estrategia III, el porcentual de pacientes vacunados contra INF fue de 35,8% y contra PNM fue de 2,5%. CONCLUSIÓN: La tasa de vacunación contra INF y PNM en pacientes con IC es muy baja y aun menor en aquellos descompensados atendidos en servicio de emergencia.BACKGROUND: Heart failure (HF is associated with frequent decompensation and admissions to the emergency service. Influenza (INF and Pneumococcal (pneumonia vaccinations are recommended in the guidelines, however, respiratory infections are the third leading cause of hospitalization in heart failure. OBJECTIVE: To assess the frequency of vaccination against INF and PNM in patients with HF in government healthcare units. METHODS: An observational study carried out in Teresópolis, a mountain region in Rio de Janeiro, employed three strategies: (I study of requests for vaccine against INF and/or PNM in the Health Department of Teresópolis between 2004 and 2006; (II direct inquiry to 61 patients with heart failure treated in primary care about their vaccination status against INF and PNM; (III direct inquiry about
Full Text Available Introduction . The International Circumpolar Surveillance network is a population-based surveillance system that collects data on invasive pneumococcal disease (IPD in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first introduced in some regions of Northern Canada in 2002, followed by 10-valent (2009 and 13-valent (PCV-13 vaccines (2010. A 23-valent polysaccharide (PPV-23 vaccine was first introduced in 1988 for special populations and adults aged 65 years and older. To describe the epidemiology in the context of pneumococcal vaccination programs, we analysed surveillance data from Northern Canada from 1999 to 2010. Methods . A standardized case report form capturing demographic and clinical information was completed for all IPD cases in Northern Canada meeting the national case definition. Isolates were sent to a reference laboratory for confirmation, serotyping and antimicrobial resistance testing. Both laboratory and epidemiological data were sent to the Public Health Agency of Canada for analysis. Population denominators were obtained from Statistics Canada. Results . From 1999 to 2010, 433 IPD cases were reported (average 36 cases per year. Incidence was greatest among infants aged <2 years and among those aged 65 years and older, with an average annual incidence of 133 and 67 cases per 100,000 population, respectively. After a peak in incidence in 2008, rates among infants have declined. Incidence rates varied from 2 to 16 times greater, depending on the year, among Aboriginals compared to non-Aboriginals. Hospitalization was reported in 89% of all cases and the case fatality ratio was 6.0%. Clinical manifestations varied, with some patients reporting >1 manifestation. Pneumonia was the most common (70%, followed by bacteremia/septicaemia (30% and meningitis (8%. Approximately, 42% of cases aged <2 years in 2009 and 2010 had serotypes covered by the PCV-13. In addition, the majority (89% of serotypes isolated in cases
Farooqui, Habib; Jit, Mark; Heymann, David L; Zodpey, Sanjay
The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3-3.9 million) episodes of severe pneumonia and 0.35 million (0.31-0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49-0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92-119 thousand) pneumococcal deaths occurred in India. The top contributors to India's pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results
Full Text Available The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3-3.9 million episodes of severe pneumonia and 0.35 million (0.31-0.40 million all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths Madhya Pradesh (6.6% children, 9% cases, 12% deaths, and Rajasthan (6.6% children, 8% cases, 11% deaths. Further, we estimated that 0.56 million (0.49-0.64 million severe episodes of pneumococcal pneumonia and 105 thousand (92-119 thousand pneumococcal deaths occurred in India. The top contributors to India's pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our
Farooqui, Habib; Jit, Mark; Heymann, David L.; Zodpey, Sanjay
The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our
Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik
Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248
Nasal immunization of mice with Lactobacillus casei expressing the Pneumococcal Surface Protein A: induction of antibodies, complement deposition and partial protection against Streptococcus pneumoniae challenge.
Campos, Ivana B; Darrieux, Michelle; Ferreira, Daniela M; Miyaji, Eliane N; Silva, Débora A; Arêas, Ana Paula M; Aires, Karina A; Leite, Luciana C C; Ho, Paulo L; Oliveira, Maria Leonor S
Strategies for the development of new vaccines against Streptococcus pneumoniae infections try to overcome problems such as serotype coverage and high costs, present in currently available vaccines. Formulations based on protein candidates that can induce protection in animal models have been pointed as good alternatives. Among them, the Pneumococcal Surface Protein A (PspA) plays an important role during systemic infection at least in part through the inhibition of complement deposition on the pneumococcal surface, a mechanism of evasion from the immune system. Antigen delivery systems based on live recombinant lactic acid bacteria (LAB) represents a promising strategy for mucosal vaccination, since they are generally regarded as safe bacteria able to elicit both systemic and mucosal immune responses. In this work, the N-terminal region of clade 1 PspA was constitutively expressed in Lactobacillus casei and the recombinant bacteria was tested as a mucosal vaccine in mice. Nasal immunization with L. casei-PspA 1 induced anti-PspA antibodies that were able to bind to pneumococcal strains carrying both clade 1 and clade 2 PspAs and to induce complement deposition on the surface of the bacteria. In addition, an increase in survival of immunized mice after a systemic challenge with a virulent pneumococcal strain was observed.
Wagner, Abram L; Boulton, Matthew L; Sun, Xiaodong; Mukherjee, Bhramar; Huang, Zhuoying; Harmsen, Irene A; Ren, Jia; Zikmund-Fisher, Brian J
In China, the measles vaccine is offered for free whereas the pneumococcal vaccine is a for-fee vaccine. This difference has the potential to influence how caregivers evaluate whether a vaccine is important or necessary for their child, but it is unclear if models of health behavior, such as the Health Belief Model, reveal the same associations for different diseases. This study compares caregiver perceptions of different diseases (measles, pneumonia and meningitis); and characterizes associations between Health Belief Model constructs and both pneumococcal vaccine uptake and perceived vaccine necessity for pneumonia, measles, and meningitis. Caregivers of infants and young children between 8 months and 7 years of age from Shanghai (n = 619) completed a written survey on their perceptions of measles, pneumonia, and meningitis. We used logistic regression models to assess predictors of pneumococcal vaccine uptake and vaccine necessity. Only 25.2% of children had received a pneumococcal vaccine, although most caregivers believed that pneumonia (80.8%) and meningitis (92.4%), as well as measles (93.2%), vaccines were serious enough to warrant a vaccine. Perceived safety was strongly associated with both pneumococcal vaccine uptake and perceived vaccine necessity, and non-locals had 1.70 times higher odds of pneumonia vaccine necessity than non-locals (95% CI: 1.01, 2.88). Most factors had a similar relationship with vaccine necessity, regardless of disease, indicating a common mechanism for how Chinese caregivers decided which vaccines are necessary. Because more caregivers believed meningitis needed a vaccine than pneumonia, health care workers should emphasize pneumococcal vaccination's ability to protect against meningitis.
South Africa's industry accounts for approximately 49% of agricultural gross domestic product, with an average annual turnover of US$13 billion. Vaccines for healthier livestock Vaccination is a critical tool to help reduce the number of livestock losses to viral infections. This project builds on the Canadian International Food ...
Rijn, van P.A.; Daus, F.J.; Maris-Veldhuis, M.A.; Feenstra, Femke; Gennip, van H.G.P.
Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV) transmitted by biting midges of the Culicoides genus. Outbreaks have been controlled successfully by vaccination, however, currently available BT vaccines have several shortcomings. Recently, we have developed BT Disabled
Di Sabatino, Antonio; Lenti, Marco Vincenzo; Tinozzi, Francesco Paolo; Lanave, Marina; Aquino, Ivana; Klersy, Catherine; Marone, Piero; Marena, Carlo; Pietrabissa, Andrea; Corazza, Gino Roberto
Splenectomy is a well-recognised risk factor for life-threatening overwhelming post-splenectomy infection (OPSI). To prevent OPSI, immunisations against encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae) and influenza virus are recommended. However, there is still a lack of uniformity and poor compliance with these recommendations. Following a local physicians' awareness campaign regarding the importance of vaccine prophylaxis of splenectomised patients, we aimed to register vaccination coverage, mortality and infection rates in all patients who underwent splenectomy at our hospital, over a six-year time span. Reasons for splenectomy, patients' compliance with vaccinations, mortality and infectious events were recorded. The reasons for splenectomy in the 216 identified patients (mean age 58.2 ± 14; M:F ratio 1.4:1) were haematologic disorders (38.8%), solid tumours (28.7%), traumatic rupture (22.7%) and other causes (9.7%). A total of 146 patients (67.6%) received at least one of the four vaccines. Overall, the mortality rate was significantly greater in unvaccinated compared to vaccinated patients (p splenectomy the statistical significance was lost (p = 0.085) due to the burden of solid tumour-related mortality. Among the 21 reported cases of OPSI, eight were fatal and five were potentially vaccine-preventable. Our results show that two-thirds of splenectomised patients comply with vaccine prophylaxis. Future interventional studies or ad hoc registries might overcome barriers to vaccination or intentional non-compliance.
Ana Marli Christovam Sartori
Full Text Available ABSTRACT OBJECTIVE To describe methods and challenges faced in the health impact assessment of vaccination programs, focusing on the pneumococcal conjugate and rotavirus vaccines in Latin America and the Caribbean. METHODS For this narrative review, we searched for the terms "rotavirus", "pneumococcal", "conjugate vaccine", "vaccination", "program", and "impact" in the databases Medline and LILACS. The search was extended to the grey literature in Google Scholar. No limits were defined for publication year. Original articles on the health impact assessment of pneumococcal and rotavirus vaccination programs in Latin America and the Caribbean in English, Spanish or Portuguese were included. RESULTS We identified 207 articles. After removing duplicates and assessing eligibility, we reviewed 33 studies, 25 focusing on rotavirus and eight on pneumococcal vaccination programs. The most frequent studies were ecological, with time series analysis or comparing pre- and post-vaccination periods. The main data sources were: health information systems; population-, sentinel- or laboratory-based surveillance systems; statistics reports; and medical records from one or few health care services. Few studies used primary data. Hospitalization and death were the main outcomes assessed. CONCLUSIONS Over the last years, a significant number of health impact assessments of pneumococcal and rotavirus vaccination programs have been conducted in Latin America and the Caribbean. These studies were carried out few years after the programs were implemented, meet the basic methodological requirements and suggest positive health impact. Future assessments should consider methodological issues and challenges arisen in these first studies conducted in the region.
Sampson, Joshua N; Hildesheim, Allan; Herrero, Rolando; Gonzalez, Paula; Kreimer, Aimee R; Gail, Mitchell H
Cervical cancer is a leading cause of cancer mortality in women worldwide. Human papillomavirus (HPV) types 16 and 18 cause about 70% of all cervical cancers. Clinical trials have demonstrated that three doses of either commercially available HPV vaccine, Cervarix ® or Gardasil ®, prevent most new HPV 16/18 infections and associated precancerous lesions. Based on evidence of immunological non-inferiority, 2-dose regimens have been licensed for adolescents in the United States, European Union, and elsewhere. However, if a single dose were effective, vaccine costs would be reduced substantially and the logistics of vaccination would be greatly simplified, enabling vaccination programs in developing countries. The National Cancer Institute (NCI) and the Agencia Costarricense de Investigaciones Biomédicas (ACIB) are conducting, with support from the Bill & Melinda Gates Foundation and the International Agency for Research on Cancer (IARC), a large 24,000 girl study to evaluate the efficacy of a 1-dose regimen. The first component of the study is a four-year non-inferiority trial comparing 1- to 2-dose regimens of the two licensed vaccines. The second component is an observational study that estimates the vaccine efficacy (VE) of each regimen by comparing the HPV infection rates in the trial arms to those in a contemporaneous survey group of unvaccinated girls. In this paper, we describe the design and statistical analysis for this study. We explain the advantage of defining non-inferiority on the absolute risk scale when the expected event rate is near 0 and, given this definition, suggest an approach to account for missing clinic visits. We then describe the problem of estimating VE in the absence of a randomized placebo arm and offer our solution. Copyright © 2018. Published by Elsevier Inc.
Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm
Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge. Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers. Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity.
A Lactococcus lactis BFE920 feed vaccine expressing a fusion protein composed of the OmpA and FlgD antigens from Edwardsiella tarda was significantly better at protecting olive flounder (Paralichthys olivaceus) from edwardsiellosis than single antigen vaccines.
Beck, Bo Ram; Lee, Soon Ho; Kim, Daniel; Park, Ji Hye; Lee, Hyun Kyung; Kwon, San-Sung; Lee, Kwan Hee; Lee, Jae Il; Song, Seong Kyu
Edwardsiellosis is a major fish disease that causes a significant economic damage in the aquaculture industry. Here, we assessed vaccine efficacy after feeding oral vaccines to olive flounder (Paralichthys olivaceus), either L. lactis BFE920 expressing Edwardsiella tarda outer membrane protein A (OmpA), flagellar hook protein D (FlgD), or a fusion antigen of the two. Feed vaccination was done twice with a one-week interval. Fish were fed regular feed adsorbed with the vaccines. Feed vaccination was given over the course of one week to maximize the interaction between the feed vaccines and the fish intestine. Flounder fed the vaccine containing the fusion antigen had significantly elevated levels T cell genes (CD4-1, CD4-2, and CD8α), type 1 helper T cell (Th1) subset indicator genes (T-bet and IFN-γ), and antigen-specific antibodies compared to the groups fed the single antigen-expressing vaccines. Furthermore, the superiority of the fusion vaccine was also observed in survival rates when fish were challenged with E. tarda: OmpA-FlgD-expressing vaccine (82.5% survival); FlgD-vaccine (55.0%); OmpA-vaccine (50%); WT L. lactis BFE920 (37.5%); Ctrl (10%). In addition, vaccine-fed fish exhibited increased weight gain (∼20%) and a decreased feed conversion ratio (∼20%) during the four week vaccination period. Flounder fed the FlgD-expressing vaccine, either the single or the fusion form, had significantly increased expression of TLR5M, IL-1β, and IL-12p40, suggesting that the FlgD may be a ligand of olive flounder TLR5M receptor or closely related to the TLR5M pathway. In conclusion, the present study demonstrated that olive flounder fed L. lactis BFE920 expressing a fusion antigen composed of E. tarda OmpA and FlgD showed a strong protective effect against edwardsiellosis indicating this may be developed as an E. tarda feed vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.
Abram L Wagner
Full Text Available BACKGROUND: Haemophilus influenzae type b (Hib vaccine and pneumococcal conjugate vaccine (PCV are relatively expensive, newly introduced vaccines in China. This study evaluates the impact of residency and urbanicity on Hib vaccine and PCV coverage for children aged 2 to 7 years living in Shanghai, China, in August 2012. METHODS: In this exploratory cohort study, a sample of children aged 2 to 7 years, all of whom were eligible to have received the complete series of Hib vaccine and PCV, was obtained from the Shanghai Immunization Program Information System. Three measures of vaccination coverage for Hib vaccine and PCV were examined: dose 1 coverage, series completion, and timeliness of dose 1 vaccination. Multivariable binomial regression was used to estimate the difference in vaccination coverage between locals and the floating population. RESULTS: Dose 1 coverage was 50.9% for Hib vaccine and 11.4% for PCV for the 28,141 abstracted pediatric records. For both vaccines, dose 1 coverage was higher in locals than in the floating population. The disparity in coverage between locals and the floating population was greater in suburban areas than urban areas. Of all children who received dose 1, 79.7% completed the Hib vaccine series, and 91.3% completed the PCV series. Timely dose 1 coverage was 8.2% for Hib vaccine and 0.5% for PCV. CONCLUSION: Low vaccination coverage and extremely low levels of timely dose 1 vaccination indicate that current vaccination efforts are inadequate to reduce the burden of Hib and pneumococcal disease among Chinese children, especially infants. Government funding of the Hib vaccine and PCV through the Expanded Program on Immunization would increase uptake and could also ensure that improvement in the timeliness of administration and series completion is targeted for all demographic groups.
Palmer, Gene A; Brogdon, Jennifer L; Constant, Stephanie L; Tattersall, Peter
An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.
Chao, Anne; Huang, Yhu-Chering; Chang, Yao-Lung; Wang, Tzu-Hao; Chang, Shuenn-Dyh; Wu, Ting-Shu; Wu, Tsu-Lan; Chao, An-Shine
To determine the prevalence of preexisting antibodies against the pandemic 2009 Influenza A (H1N1) virus in pregnant women and to evaluate the seroprotection of the mothers and infants by a single injection of monovalent vaccine during the pandemic. Seropositivity rate of H1N1 among the nonvaccinated were compared with the vaccinated women. A single dose of vaccine, either nonadjuvanted AdimFlu-S or MF59-adjuvanted vaccine, was injected to the voluntarily vaccinated group. Maternal and cord blood sera were collected to evaluate the antibody response of the H1N1 virus. Seropositivity was defined as a hemagglutination inhibition titer to H1N1 (A/Taiwan/126/09) ≥ 1:40. A total of 210 healthy, singleton, pregnant women were enrolled between January 2010 and May 2010. Seropositivity (≥ 1:40) of maternal hemagglutination inhibition was significantly higher in the vaccinated group (78%) than the nonvaccinated group (9.5%); 41.6% (20/48) of seropositive titers were >1:80. In nine vaccinated cases resulting in negative serum titers (75% could be achieved in the paired maternal and cord serum samples by a single injection of monovalent H1N1 vaccine. Copyright © 2013. Published by Elsevier B.V.
Edmond J Remarque
Full Text Available Plasmodium falciparum: apical membrane antigen 1 (AMA1 is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 µg of a single allele AMA1 antigen (FVO formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naïve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i Antibody responses to various allelic variants, (ii Domain specificity, (iii Avidity, (iv IgG subclass levels, by ELISA and (v functionality of antibody responses by Growth Inhibition Assay (GIA. About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains.ClinicalTrials.gov NCT00730782.
Awa L Mendy
Full Text Available The currently used Streptococcus pneumoniae vaccines have had a significant impact on the pneumococcal diseases caused by the serotypes they cover. Their limitations have stimulated a search for alternate vaccines that will cover all serotypes, be affordable and effective in young children. Pneumococcal protein antigens are potential vaccine candidates that may meet some of the shortfalls of the current vaccines. Thus, this study aimed to determine the relationship between antibodies against pneumococcal protein antigens and nasopharyngeal carriage in infants.One hundred and twenty mother-infant pairs were enrolled into the study. They had nasopharyngeal swabs(NPS taken at birth and every two weeks for the first eight weeks after delivery, and blood samples were obtained at birth and every four weeks for the first eight weeks after delivery. Nasopharyngeal carriage of S. pneumoniae was determined from the NPS and antibodies against the pneumococcal proteins CbpA, PspA and rPly were measured in the blood samples.The S. pneumoniae carriage rate in infants increased to that of mothers by eight weeks of age. The odds of carriage in infants was 6.2 times (95% CI: 2.0-18.9 higher when their mothers were also carriers. Bacterial density in infants was lower at birth compared to their mothers (p = 0.004, but increased with age and became higher than that of their mothers at weeks 4 (p = 0.009, 6 (p = 0.002 and 8 (p<0.0001. At birth, the infants' antibodies against CbpA, and rPly pneumococcal protein antigens were similar, but that of PspA was lower (p<0.0001, compared to their mothers. Higher antibody concentrations to CbpA [OR (95% CI: 0.49 (0.26-0.92, p = 0.03], but not PspA and rPly, were associated with protection against carriage in the infants.Naturally induced antibodies against the three pneumococcal protein antigens were transferred from mother to child. The proportion of infants with nasopharyngeal carriage and the bacterial density of S
Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Sangare, Lassana; Yaméogo, Issaka; Sawadogo, Guetawendé; Ouédraogo, Abdoul-Salam; Hema-Ouangraoua, Soumeya; McGee, Lesley; Srinivasan, Velusamy; Aké, Flavien; Congo-Ouédraogo, Malika; Sanou, Soufian; Ba, Absatou Ky; Novak, Ryan T.; Van Beneden, Chris
Background Following introduction of Haemophilus influenzae type b vaccine in 2006 and serogroup A meningococcal conjugate vaccine in 2010, Streptococcus pneumoniae (Sp) became the leading cause of bacterial meningitis in Burkina Faso. We describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the pediatric routine immunization program in October 2013. Methods Nationwide population-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Sp infections are confirmed by culture, real-time polymerase chain reaction (rt-PCR), or latex agglutination, and CSF serotyped using real-time and conventional PCR. We calculated incidence rates in cases per 100,000 persons, adjusting for age and proportion of cases with CSF tested at national reference laboratories, and case fatality ratios (CFR). Results During 2011–2013, 1,528 pneumococcal meningitis cases were reported. Average annual adjusted incidence rates were 26.9 (meningitis occurred among children aged <1 year. The majority of cases were due to PCV13-associated serotypes; introduction of PCV13 should substantially decrease this burden. PMID:27832151
The administration of a single dose of a multivalent (DHPPiL4R) vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus
Stephen Wilson; Joanna Illambas; Elisabeth Siedek; Anne Thomas; Vickie King; Catrina Stirling; Edita Plevová; Jeremy Salt; Gordon Sture
Four challenge studies following vaccination of dogs with a multivalent vaccine containing canine parvovirus (CPV-2b), adenovirus (CAV-1/-2) and distemper (CDV) are described. Six week old puppies received a single vaccination while non-vaccinated control dogs received water. In each respective trial, groups of dogs were challenged 21 days after vaccination with heterologous viral isolates. Clinical observations, rectal temperature measurements, and blood and swab samples for analysis were co...
Ülkü Aka Aktürk
Full Text Available Background: Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. Aims: To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Study Design: Multi-centre cross-sectional study. Methods: Patients admitted to the chest diseases clinics of six different centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of Chronic obstructive pulmonary disease according to the Global initiative for chronic obstructive lung disease criteria, who were in a stable condition were included in the study. The survey, which included demographic characteristics, socio-economic status, severity of disease and vaccination information, was first tested on a small patient population before the study. The survey was completed by the investigators after obtaining written informed consent. Results: The average age of the 296 included patients was 66.3±9.3 years and 91.9% were male. Of these, 36.5% had the influenza vaccination and 14.1% had the pneumococcal vaccination. The most common reason for not being vaccinated was ‘no recommendation by doctors’: 57.2% in the case of influenza vaccinations, and 46.8% in the case of pneumococcal vaccinations. Both vaccination rates were significantly higher in those patients with comorbidities (influenza vaccination p0.05. Vaccination rates were significantly higher in those with a white-collar occupation and higher education level, and who presented to a university hospital (p<0.001. Conclusion: Medical professionals do not request vaccinations as often as the International Guidelines suggest for chronic obstructive pulmonary disease patients. Awareness of the importance of these vaccinations among both doctors and patients
Chapman, Stephen J; Khor, Chiea C; Vannberg, Fredrik O; Rautanen, Anna; Segal, Shelley; Moore, Catrin E; Davies, Robert J O; Day, Nicholas P; Peshu, Norbert; Crook, Derrick W; Berkley, James A; Williams, Thomas N; Scott, J Anthony; Hill, Adrian V S
The proinflammatory transcription factor nuclear factor-kappaB (NF-κB) plays a central role in host defence against pneumococcal disease. Both rare mutations and common polymorphisms in the NFKBIA gene encoding the NF-κB inhibitor IκB-α associate with susceptibility to bacterial disease, but the possible role of polymorphisms within the related IκB-ζ gene NFKBIZ in the development of invasive pneumococcal disease has not previously been reported. To investigate this further, we examined the frequencies of 22 single-nucleotide polymorphisms spanning NFKBIZ in two case-control studies, comprising UK Caucasian (n=1008) and Kenyan (n=723) individuals. Nine polymorphisms within a single UK linkage disequilibrium block and all four polymorphisms within the equivalent, shorter Kenyan linkage disequilibrium block displayed either significant association with invasive pneumococcal disease or a trend towards association. For each polymorphism, heterozygosity was associated with protection from invasive pneumococcal disease when compared to the combined homozygous states (e.g. for rs600718, Mantel-Haenszel 2×2 χ2=7.576, P=0.006, OR=0.67, 95% CI for OR: 0.51-0.88; for rs616597, Mantel-Haenszel 2×2 χ2=8.715, P=0.003, OR=0.65, 95% CI: 0.49-0.86). We conclude that multiple NFKBIZ polymorphisms associate with susceptibility to invasive pneumococcal disease in humans. The study of multiple populations may aid fine-mapping of associations within extensive regions of strong linkage disequilibrium (‘transethnic mapping’). PMID:19798075
Auranen, Kari; Syrjänen, Ritva; Leino, Tuija; Kilpi, Terhi
For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media.
Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C
The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine
Setchanova, Lena Petrova; Alexandrova, Alexandra; Dacheva, Daniela; Mitov, Ivan; Kaneva, Radka; Mitev, Vanio
A pneumococcal conjugate vaccine (PCV10) was introduced in Bulgarian national immunization program since April 2010. Clonal composition based on pulsed-field gel electrophoresis and multilocus sequence typing genotyping of 52 serotype 19A Streptococcus pneumoniae isolates was analyzed. These were invasive and respiratory isolates collected between 1992 and 2013 from both children (78.8% clone. The most frequent sequence type (ST) was ST230 (48.1%) and together with four other closely related STs (15.4%), belonging to ST1611, ST276, ST7466, and ST2013, which were single- and double-locus variants; they were included in the main CC230. The disappearance of highly drug-resistant ST663 clone and emergence of new clones as CC320 and CC199 was also observed among the rest 19A isolates. A comparison of clonal composition between invasive and noninvasive isolates did not show a great genetic diversity among both kinds of isolates. Continuous surveillance of serotype 19A population following the introduction of PCV10 is essential to evaluate the impact of the vaccine on the epidemiology of this serotype.